Affinage

CSPG4

Chondroitin sulfate proteoglycan 4 · UniProt Q6UVK1

Length
2322 aa
Mass
250.5 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSPG4 (NG2/HMW-MAA) is a large transmembrane chondroitin sulfate proteoglycan that functions as a multifunctional cell-surface scaffold coupling extracellular matrix and growth-factor cues to intracellular survival, proliferation, and motility signaling (PMID:23559515, PMID:38309500). It serves as a host receptor for Clostridioides difficile toxin TcdB: the binding interface maps to discontinuous regions spanning the junction of the toxin's translocation and CROP domains, requires at least three CROP short repeats, is potentiated by extracellular Ca2+ acting on the CSPG4 protein core, and is blocked by the therapeutic antibody bezlotoxumab; CSPG4-knockout mice are protected from colonic damage, and the chondroitin sulfate (CS) chains accelerate toxin cell entry after surface binding (PMID:34145250, PMID:28842504, PMID:38470254). In epithelial tissue, junctional and fibroblast-shed CSPG4 provides receptor access along the colonic crypt-surface axis (PMID:37747247). As an adhesion and signaling receptor, CSPG4 engages matrix ligands including collagen type VI and the basement-membrane proteoglycan perlecan to drive actin polymerization, adhesion, and motility through PI-3K and FAK signaling (PMID:29462330, PMID:23559515), and sustains FAK/AKT/ERK and cyclin D1 signaling that supports tumor cell proliferation, survival, migration, and angiogenesis across melanoma, mesothelioma, sarcoma, and glioma (PMID:22021902, PMID:22893632, PMID:21829586). Its CS modification acts as a molecular switch: CS-bearing CSPG4 maintains glioma-initiating cells, whereas CS removal permits CSPG4 binding to integrin αV and activation of integrin-ERK signaling that promotes differentiation (PMID:38309500). CSPG4 abundance is set transcriptionally by SoxE/bHLH factors acting through an NG2-glia-specific intronic enhancer, by MRTF-SRF, by redox-regulated SP-1, by EGR1, and by Hippo signaling (PMID:30306660, PMID:33727640, PMID:34952462, PMID:31006910, PMID:36972308). Loss-of-function studies establish physiological roles in OPC morphogenesis, trophoblast invasion and placentation, angiogenesis during muscle regeneration, and cartilage mechanical homeostasis via mechanically activated ERK1/2 (PMID:39566199, PMID:36634519, PMID:40769519, PMID:36685663). A germline CSPG4-A131T missense mutation in iPSC-derived oligodendrocyte precursors causes aberrant protein processing, mislocalization, abnormal morphology, and impaired myelination potential, linking CSPG4 dysfunction to disease (PMID:29302076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2013 High

    Established that CSPG4 is not merely a passive matrix component but an adhesion receptor that transduces matrix engagement into survival and motility signaling, defining its mechanistic role in tumor cells.

    Evidence Domain-deletion and dominant-negative NG2 mutants, purified collagen VI fragments, RNAi, and xenografts mapping NG2-Col VI binding to PI-3K activation

    PMID:23559515

    Open questions at the time
    • Did not define the membrane-proximal signaling complex linking CSPG4 to PI-3K
    • Generality beyond sarcoma not established in this study
  2. 2018 High

    Resolved how CSPG4 transcription is restricted to NG2 glia versus pericytes, identifying the cis-regulatory logic that establishes cell-type-specific expression.

    Evidence 1.45 kb intronic enhancer reporter assays, EGFP transgenic mice, and mutagenesis of SoxE/bHLH binding elements

    PMID:30306660

    Open questions at the time
    • Did not identify the specific SoxE/bHLH family members in vivo
    • Did not address how pericyte CSPG4 is driven
  3. 2018 Medium

    Extended CSPG4's ligand repertoire to perlecan and to FGF1, framing it as a surface reservoir for matrix and growth-factor ligands.

    Evidence Immunopurification with perlecan domain-mapping and actin assays; APEX2-FGF1 proximity labeling with mass spectrometry and colocalization

    PMID:29462330 PMID:29812912

    Open questions at the time
    • FGF1 storage function not functionally proven downstream
    • Whether perlecan and FGF1 binding involve overlapping CSPG4 regions unknown
  4. 2021 High

    Solved the structural basis of CSPG4 as the TcdB receptor and validated it in vivo, transforming a cell-surface marker into a defined toxin-host interface with therapeutic relevance.

    Evidence Cryo-EM of the TcdB-CSPG4 complex, site-directed mutagenesis disrupting binding, CSPG4-knockout mice, and bezlotoxumab competition

    PMID:28842504 PMID:34145250

    Open questions at the time
    • Did not resolve the CS contribution to entry kinetics
    • Relative in vivo contribution versus other TcdB receptors unquantified
  5. 2021 Medium

    Defined multiple transcriptional inputs (MRTF-SRF, redox-regulated SP-1) that tune CSPG4 abundance in smooth muscle and glia, connecting actin dynamics and cellular redox state to receptor expression.

    Evidence MRTF overexpression and SRF silencing with promoter reporters and CCG-1423; Grx2c manipulation with SP-1 redox/DNA-binding analysis across cell, ex vivo, and zebrafish models

    PMID:33727640 PMID:34952462

    Open questions at the time
    • Cross-talk between MRTF-SRF and SP-1 inputs not integrated
    • Direct redox modification site on SP-1 controlling CSPG4 not mapped
  6. 2023 Medium

    Connected receptor access and expression control in vivo, showing fibroblast-shed CSPG4 and Hippo-dependent transcription govern epithelial susceptibility to TcdB.

    Evidence Immunofluorescence of colonic crypt-surface axis; TcdB-resistance selection, CRISPR deletion of Hippo regulators, chemical modulation, and mouse disease protection

    PMID:36972308 PMID:37747247

    Open questions at the time
    • Identity of the protease shedding epithelial CSPG4 not defined
    • Direct Hippo transcriptional regulators binding the CSPG4 locus not mapped
  7. 2024 High

    Showed that the chondroitin sulfate modification acts as a binary switch controlling CSPG4 partner choice, with de-CS-modified CSPG4 binding integrin αV to drive differentiation versus CS-bearing CSPG4 maintaining stem-like state.

    Evidence ChondroitinaseABC and XYLT1/CSPG4 knockdown, co-IP with integrin αV, cyclic-RGD inhibition, and proteo-genomics of patient-derived glioma-initiating cells

    PMID:38309500

    Open questions at the time
    • Enzyme/signal controlling CS removal physiologically not identified
    • Whether this switch operates in non-glioma contexts unknown
  8. 2024 Medium

    Genetically isolated a specific physiological function of CSPG4, distinguishing OPC morphogenesis from differentiation and myelination.

    Evidence cspg4 loss-of-function zebrafish with morphology, differentiation, and myelin sheath quantification

    PMID:39566199

    Open questions at the time
    • Molecular effector of morphogenesis downstream of CSPG4 not defined
    • Mammalian conservation of this restricted phenotype untested
  9. 2025 Medium

    Proposed a mechanotransduction mechanism whereby neuronal NLGN3 binds CSPG4 and triggers ADAM10 shedding, altering membrane tension to activate PIEZO1 and maintain undifferentiated, proliferative states.

    Evidence Biochemical NLGN3-CSPG4 binding, ADAM10 shedding, PIEZO1 channel and membrane-tension measurements, glioma proliferation assays (preprint)

    PMID:40791371

    Open questions at the time
    • Preprint, not yet peer reviewed
    • Direct causal chain from shedding to PIEZO1 activation not fully reconstituted
    • In vivo requirement untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CSPG4's diverse inputs—CS-state, matrix ligands, growth factors, and mechanical force—are integrated at the cytoplasmic tail into a unified signaling output remains undefined.
  • No defined cytoplasmic signaling complex linking CSPG4 to ERK/AKT
  • No structural model of the full-length receptor with its CS chains
  • Quantitative hierarchy among transcriptional regulators in any single cell type unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0001618 virus receptor activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0008289 lipid binding 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1643685 Disease 2
Partners
ADAM10COL6FGF1HSPG2ITGAVNLGN3TCDB

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Cryo-EM structure of TcdB-CSPG4 complex revealed that CSPG4 is a receptor for C. difficile toxin TcdB, with a unique binding site composed of multiple discontinuous regions across TcdB. CSPG4-knockout mice showed reduced colonic tissue damage during C. difficile infections, and mutations selectively disrupting CSPG4 binding reduced TcdB toxicity in mice. Bezlotoxumab blocks CSPG4 binding to TcdB via an allosteric mechanism. Cryo-EM structure determination, site-directed mutagenesis, CSPG4-knockout mouse model, in vivo toxicity assays Nature communications High 34145250
2017 The CSPG4-binding site on TcdB maps to a region at the junction of the translocation and CROP domains, requiring at least three CROP short repeats for binding and full toxicity on CSPG4-expressing cells. The anti-TcdB antibody bezlotoxumab prevents CSPG4 binding by overlapping with the CSPG4-binding site in the first three short repeats. C-terminal truncation series, receptor-binding mutant screen, cell intoxication assays, competitive binding assays The Journal of biological chemistry High 28842504
2024 Extracellular Ca2+ promotes preferential TcdB binding to CSPG4 (protein core), while the chondroitin sulfate (CS) moiety of CSPG4 does not enhance Ca2+-mediated binding but instead influences the rate of TcdB cell entry after surface binding. TcdB receptor-binding mutants, cell lines with varied receptor profiles, Ca2+ manipulation assays, binding and cytotoxicity assays mSphere Medium 38470254
2023 Nectin-3 and shed forms of CSPG4 (shed by fibroblasts along the crypt-surface axis) serve as epithelial cell receptors for C. difficile TcdB on colonic epithelial cells, with CSPG4 localized at epithelial cell junctions as visualized by immunofluorescence microscopy on colonic tissue. Immunofluorescence microscopy on colonic tissue sections mBio Medium 37747247
2018 CSPG4 binds to the basement membrane proteoglycan perlecan via hydrophobic protein-protein interactions involving multiple sites on perlecan including the C-terminal region. This CSPG4-perlecan interaction supports cell adhesion and actin polymerization. Immunopurification of CSPG4 from melanoma cell lines, co-complex formation assay, mechanistic domain-mapping with purified perlecan fragments, actin polymerization assay Journal of biochemistry Medium 29462330
2013 NG2/CSPG4 interacts with collagen type VI (Col VI) through reciprocal binding sites identified using dominant-negative NG2 mutants and purified Col VI domain fragments. NG2-Col VI binding triggers activation of PI-3K-dependent cell survival and cell adhesion/migration signaling pathways, controlling sarcoma cell adhesion and motility. Dominant-negative NG2 mutant cells, purified Col VI domain fragments, RNAi knockdown, ectopic transduction of full-length/deletion NG2 constructs, in vitro adhesion/motility assays, xenograft models Journal of molecular cell biology High 23559515
2011 CSPG4-specific antibody (scFv-FcC21) inhibits tumor cell growth and migration by blocking activation of ERK (required for growth) and focal adhesion kinase (FAK) signaling (required for migration) in CSPG4-positive tumor cells. Phage display antibody generation, in vitro growth and migration assays, signaling pathway analysis (ERK and FAK phosphorylation), in vivo xenograft tumor growth assay Cancer research Medium 22021902
2010 CSPG4-specific mAb 225.28 inhibits TNBC cell growth, adhesion, and migration in vitro, with antitumor mechanisms including increased apoptosis, reduced mitotic activity, decreased tumor vascularity, and reduced activation of survival/proliferation/metastasis signaling pathways. In vitro growth, adhesion, and migration assays; apoptosis assays; in vivo metastasis and orthotopic xenograft models; signaling pathway analysis Journal of the National Cancer Institute Medium 20852124
2012 CSPG4 mediates mesothelioma cell adhesion via engagement of extracellular matrix (ECM); mAb TP41.2 blockade of CSPG4 decreases phosphorylation of FAK and AKT, reduces cyclin D1 expression, and induces apoptosis, establishing CSPG4 as a key upstream regulator of FAK/AKT/cyclin D1 signaling in mesothelioma. CSPG4 antibody blockade, adhesion assays, immunoblotting for FAK and AKT phosphorylation, cyclin D1 expression, apoptosis assays, in vivo SCID mouse xenograft Clinical cancer research Medium 22893632
2011 NG2/CSPG4 overexpression in GBM cells increases tumor growth rate, angiogenesis, and vascular permeability in vivo. NG2 knockdown (via lentiviral shRNA) in patient-derived GBM xenografts and melanoma tumors reduced tumor growth, oedema, and angiogenesis, and normalized vascular function while increasing invasion. NG2-overexpressing GBM xenografts, lentiviral shRNA knockdown in intracranial patient GBM xenografts and subcutaneous melanoma tumors, tumor growth measurements, vascular permeability and angiogenesis assays PloS one Medium 21829586
2017 NG2/CSPG4 knockdown in established soft-tissue sarcoma cells decreased tumor volume by ~two-thirds and cell proliferation by 50%; NG2/CSPG4 deletion at tumor initiation paradoxically produced larger tumors associated with downregulation of insulin-like growth factor binding protein (Igfbp) genes, indicating stage-dependent and divergent roles for NG2/CSPG4 in sarcoma. shRNA knockdown in human sarcoma xenografts, autochthonous mouse sarcoma model with conditional Ng2/Cspg4 deletion, NG2 antibody immunotherapy, gene expression profiling The Journal of biological chemistry Medium 29196603
2019 Furanodienone (FUR) suppresses CSPG4 expression in temozolomide-resistant GBM cells by inhibiting EGR1-dependent transcription of CSPG4, thereby downregulating CSPG4-Akt-ERK signaling, suppressing inflammatory responses, and activating caspase-dependent apoptosis. In vitro cytotoxicity assays, immunofluorescence, dual-luciferase reporter assay for EGR1-mediated CSPG4 transcription, western blotting for pathway components Phytotherapy research Medium 31006910
2023 Hippo signaling pathway regulates CSPG4 expression: TcdB-resistant HeLa cells that lost CSPG4 mRNA showed correlated changes in Hippo and estrogen signaling pathways. CRISPR-mediated deletion of key Hippo transcriptional regulators and chemical modulation altered CSPG4 expression. Pharmacological inactivation of Hippo (XMU-MP-1) protected mice from C. difficile disease. TcdB-resistance selection, mRNA expression profiling, integrated pathway analysis, CRISPR deletion of Hippo pathway regulators, chemical modulation, mouse C. difficile disease model PLoS pathogens Medium 36972308
2021 NG2/CSPG4 expression in smooth muscle cells is regulated by myocardin-related transcription factors (MRTFs: MYOCD, MRTF-A/MKL1, MRTF-B/MKL2) acting through serum response factor (SRF). MRTF overexpression increased CSPG4 mRNA and protein; SRF silencing reduced CSPG4 transcript levels; CSPG4 responded to MRTF-SRF inhibitor CCG-1423 and to actin dynamics. Bioinformatics correlation, MRTF overexpression in human smooth muscle cells, SRF silencing, promoter reporter assays, pharmacological inhibition with CCG-1423 Scientific reports Medium 33727640
2021 The cytosolic isoform of Glutaredoxin 2 (Grx2c) regulates the redox state of transcription factor SP-1, modulating its binding affinity to both the promoter and an enhancer region of the CSPG4 gene, thereby increasing NG2 expression and promoting migration of NG2 glia and invasion of glioma cells. In vitro human cell lines, ex vivo mouse primary cells, in vivo zebrafish models, glioblastoma patient tissue samples, SP-1 redox state and DNA-binding analysis Redox biology Medium 34952462
2018 A 1.45 kb intronic enhancer of the mouse Cspg4 gene directs transcription to NG2 glia but not pericytes in vitro and in transgenic mice. This enhancer contains binding sites for SoxE and basic helix-loop-helix (bHLH) transcription factors, whose cooperative binding augments enhancer activity; mutations in these binding elements abolished enhancer activity. In vitro enhancer assays, EGFP reporter transgenic mice, site-directed mutagenesis of transcription factor binding elements Glia High 30306660
2018 APEX2-FGF1 proximity labeling identified CSPG4 (NG2) and CD44 as novel FGF1 binding partners at the cell surface. CSPG4 and FGF1 colocalize at the cell surface, suggesting CSPG4 acts as a storage molecule creating a reservoir of FGF1 at the cell surface. APEX2-FGF1 fusion protein proximity biotin labeling, mass spectrometry identification, co-localization imaging, signaling assay for functional validation Biochemistry Medium 29812912
2013 CSPG4 siRNA knockdown in human extravillous trophoblast (EVT) cells stimulated proliferation and decreased migration/invasion, demonstrating that CSPG4 promotes trophoblast migration and invasion. IL11 and LIF cytokines stimulated CSPG4 mRNA and protein expression in first-trimester placental villous explants. siRNA knockdown in HTR8/SVneo cells, proliferation and migration/invasion assays, cytokine stimulation of placental villous explants Placenta Medium 23953863
2023 Trophoblast-specific CSPG4 knockdown in mice caused frequent fetal loss and poor placentation, with reduced placental weight. CSPG4-knockout trophoblast cells showed inhibited proliferation and invasion, with reduced AKT and ERK phosphorylation and decreased MMP2 and MMP9 expression. Trophoblast-specific lentiviral CSPG4 knockdown mouse model, CSPG4-knockout trophoblast cell line, proliferation and invasion assays, western blotting for AKT/ERK phosphorylation and MMP expression Reproductive biology Medium 36634519
2024 Chondroitin sulfate (CS) modification on CSPG4 is required for glioma-initiating cell (GIC) maintenance. CS degradation on CSPG4 by ChondroitinaseABC induced GIC differentiation (inhibited by exogenous CS addition). During GIC differentiation, de-CS-modified CSPG4 (lacking CS chains) interacts with integrin αV, activating integrin-ERK signaling that promotes differentiation; CS-modified CSPG4 does not interact with integrin αV. ChondroitinaseABC treatment, XYLT1 knockdown, CSPG4 knockdown, co-immunoprecipitation of CSPG4 with integrin αV, cyclic-RGD inhibitor assays, proteo-genomics of patient-derived GIC clones The Journal of biological chemistry High 38309500
2022 NG2/CSPG4 is required for mechanical activation of ERK 1/2 in TMJ cartilage cells; NG2/CSPG4 knockout mice have more severe cartilage degeneration during TMJ osteoarthritis, elevated OA proteases, and suppressed OA matrix synthesis genes. In vitro, NG2/CSPG4 KO cells fail to mechanically activate ERK 1/2 under compression loading. Surgical destabilization-induced TMJ OA in NG2/CSPG4 KO mice, transcriptome and protein analysis, compression bioreactor on cell-agarose-collagen scaffolds, ERK 1/2 phosphorylation assays Frontiers in dental medicine Medium 36685663
2021 Myelin debris from damaged myelin sheaths increases NG2/CSPG4 expression in bone marrow-derived macrophages (BMDMΦ) after spinal cord injury, and these NG2/CSPG4-expressing macrophages exhibit enhanced proliferation and decreased phagocytic capacity. Spinal cord injury mouse model, identification of BMDMΦ as NG2/CSPG4 source, myelin debris stimulation in vitro with functional assays (proliferation, phagocytosis) Frontiers in cellular neuroscience Medium 33815067
2016 shRNA knockdown of CSPG4/NG2 in the JJ012 chondrosarcoma cell line reduced cell proliferation and migration, decreased gene expression of MMP3 and ADAMTS4 proteases, and increased sensitivity to doxorubicin. Stable shRNA knockdown, cell proliferation and migration assays, gene expression analysis of MMP3 and ADAMTS4, doxorubicin sensitivity assay International journal of experimental pathology Medium 27292772
2016 Using lineage tracing in mice, bone and soft-tissue sarcomas (driven by Trp53 deletion) and desmoid tumors (driven by Apc mutation) can originate from Ng2/Cspg4-expressing pericytes. β-catenin stabilization in Ng2/Cspg4+ cells caused desmoid tumors, while Trp53 deletion caused sarcomas. β-catenin signaling was inhibited in sarcomas versus precursor pericytes, and β-catenin activation inhibited sarcoma formation and growth. Cre-based lineage tracing from Ng2/Cspg4-expressing cells, conditional Trp53 deletion and Apc mutation mouse models, gene expression profiling, β-catenin activation experiments Cell reports High 27425618
2021 BRAF and MEK inhibitor treatment of BRAF-mutant melanoma cells results in markedly reduced CSPG4 protein and mRNA levels (not via increased shedding). Patient-derived matched tumor samples following kinase inhibitor therapy showed decreased numbers of CSPG4-positive cells compared to pre-therapy samples. Flow cytometry, immunofluorescence, western blotting, qPCR, measurement of CSPG4 in culture supernatants, patient tumor sample IHC Oncology reports Medium 33649790
2018 iPSC-derived oligodendrocyte precursor cells (OPCs) from carriers of the CSPG4-A131T missense mutation exhibited abnormal post-translational processing and subcellular localization of mutant NG2/CSPG4, aberrant cellular morphology, reduced viability, and impaired myelination potential. Transfection of healthy OPCs with either CSPG4-A131T or CSPG4-V901G mutants confirmed pathogenic effects on cell survival. iPSC-derived OPCs from mutation carriers, protein processing/localization assays, morphology quantification, viability assays, myelination assay, transfection of healthy OPCs with mutant constructs, in vivo diffusion tensor imaging Molecular psychiatry Medium 29302076
2025 NLGN3 (neuroligin-3) shed by neurons interacts directly with CSPG4 on glioma cells and oligodendrocyte precursor cells (OPCs), facilitating CSPG4 shedding by ADAM10. This NLGN3-CSPG4 interaction and consequent shedding alter membrane tension, activating PIEZO1 mechanosensitive channels and causing membrane depolarization, maintaining OPCs in an undifferentiated state and promoting glioma proliferation. Biochemical interaction assays (NLGN3-CSPG4 binding), ADAM10 shedding assays, PIEZO1 channel activity measurements, membrane tension assays, glioma proliferation assays bioRxivpreprint Medium 40791371
2021 Cspg4-expressing microglia represent a specific proliferative subset during neurodegeneration. Their transcriptomic signature is enriched for cell cycle genes and depleted for neuroinflammation/phagocytosis genes. Pathological α-synuclein evokes proliferation of quiescent Cspg4 microglia. Cspg4 microglia grafts show higher survival than Cspg4-negative microglia upon transplantation into adult brain with depleted endogenous microglia. Transcriptomic profiling of Cspg4 microglia subsets, PD mouse models, pathological α-synuclein stimulation, microglia transplantation assay Proceedings of the National Academy of Sciences of the United States of America Medium 36795751
2024 Zebrafish lacking cspg4 function produce normal numbers of oligodendrocyte lineage cells that undergo proper differentiation and produce myelin sheaths of normal number and length, but OPC morphology is aberrant in mutant larvae, establishing that Cspg4 specifically regulates OPC morphogenesis but is not required for OLC differentiation or myelination. cspg4 loss-of-function zebrafish model, OPC morphology quantification, OLC differentiation assessment, myelin sheath number and length measurement Differentiation; research in biological diversity Medium 39566199
2025 CSPG4 expressed on mesenchymal progenitor cells (MPCs) promotes vascular endothelial cell migration; CSPG4 KO in MPCs abrogated upregulation of endothelial migration. In CSPG4 KO rats, skeletal muscle development was perturbed with impaired angiogenesis, and muscle regeneration showed reduced CD31-positive cells at regenerating sites. CSPG4 KO rat model, muscle regeneration assay, co-culture of CSPG4-expressing vs KO MPCs with endothelial cells, endothelial cell migration assay, CD31 immunostaining Animal science journal Medium 40769519
2021 CSPG4 silencing in choroid plexus cells suppressed ferroptosis, cell adhesion function, and intracellular Ca2+ flow in a post-hemorrhagic hydrocephalus (PHH) model, suggesting CSPG4 participates in ferroptosis and Ca2+ signaling relevant to PHH pathophysiology. CSPG4 silencing in vitro cellular experiments, rat PHH models, ferroptosis assay, cell adhesion assay, intracellular Ca2+ flow measurement Advanced science Low 39686677
2021 CSPG4 expression during decidualization is required for trophoblast invasion: CSPG4 knockdown in endometrial stromal cells inhibited decidualization and subsequently inhibited trophoblast invasion. CSPG4 expression increases during artificially induced decidualization in both human cells and mouse models. siRNA knockdown of CSPG4 in endometrial stromal cells, decidualization induction assay, trophoblast invasion assay, qPCR and western blotting in pseudopregnant and pregnant mouse endometria Biology of reproduction Medium 39563514
2021 A germline V2097M variant in CSPG4 promoted cell proliferation by activating the MAPK/ERK signaling pathway via hindering ectodomain cleavage of CSPG4, as demonstrated by in vitro functional studies. Targeted sequencing, whole-exome sequencing, in vitro functional cell proliferation assays, MAPK/ERK signaling analysis, ectodomain cleavage assay Cell death & disease Low 34344877
2022 BLR (linarin derivative) increased CSPG4 gene expression and enhanced CSPG4 membrane localization, with downstream signaling protein expression associated with KDEL receptor (KDELR) activation; activated KDELR further increased phosphorylation of MAPKs. CSPG4 upregulation correlated with increased cerebral blood flow and protection from ischemic brain injury. Mouse MCAO model, RNA sequencing, coimmunoprecipitation, western blotting, laser speckle contrast imaging Oxidative medicine and cellular longevity Low 35927993

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma. Pigment cell & melanoma research 163 22004131
2010 CSPG4 protein as a new target for the antibody-based immunotherapy of triple-negative breast cancer. Journal of the National Cancer Institute 157 20852124
2004 Human high molecular weight-melanoma-associated antigen (HMW-MAA): a melanoma cell surface chondroitin sulfate proteoglycan (MSCP) with biological and clinical significance. Critical reviews in immunology 152 15588226
2010 CSPG4 in cancer: multiple roles. Current molecular medicine 102 20455858
2013 Targeting glioblastoma with NK cells and mAb against NG2/CSPG4 prolongs animal survival. Oncotarget 95 24127551
2011 Targeting the NG2/CSPG4 proteoglycan retards tumour growth and angiogenesis in preclinical models of GBM and melanoma. PloS one 94 21829586
2012 CSPG4 as a target of antibody-based immunotherapy for malignant mesothelioma. Clinical cancer research : an official journal of the American Association for Cancer Research 78 22893632
2017 The regulatory mechanisms of NG2/CSPG4 expression. Cellular & molecular biology letters 70 28536635
2015 Theranostic impact of NG2/CSPG4 proteoglycan in cancer. Theranostics 70 25767619
2017 CSPG4: a prototype oncoantigen for translational immunotherapy studies. Journal of translational medicine 64 28668095
2021 Structural basis for CSPG4 as a receptor for TcdB and a therapeutic target in Clostridioides difficile infection. Nature communications 62 34145250
2018 Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia. Molecular psychiatry 59 29302076
2014 CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA. Clinical cancer research : an official journal of the American Association for Cancer Research 59 24874834
2019 Clinical-Scale Production of CAR-T Cells for the Treatment of Melanoma Patients by mRNA Transfection of a CSPG4-Specific CAR under Full GMP Compliance. Cancers 58 31426437
2017 NG2/CSPG4 and progranulin in the posttraumatic glial scar. Matrix biology : journal of the International Society for Matrix Biology 57 29054751
2013 NG2/CSPG4-collagen type VI interplays putatively involved in the microenvironmental control of tumour engraftment and local expansion. Journal of molecular cell biology 57 23559515
2011 Functional characterization of an scFv-Fc antibody that immunotherapeutically targets the common cancer cell surface proteoglycan CSPG4. Cancer research 55 22021902
2017 Functional defects in Clostridium difficile TcdB toxin uptake identify CSPG4 receptor-binding determinants. The Journal of biological chemistry 52 28842504
2019 CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities-Merits and Challenges. International journal of molecular sciences 50 31779130
2018 The Significance of Chondroitin Sulfate Proteoglycan 4 (CSPG4) in Human Gliomas. International journal of molecular sciences 45 30213051
2018 Deficient neurotrophic factors of CSPG4-type neural cell exosomes in Alzheimer disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 44 29924942
2018 Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 44 30550356
2016 Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination. Veterinary and comparative oncology 42 27146852
2014 Reduced promoter methylation and increased expression of CSPG4 negatively influences survival of HNSCC patients. International journal of cancer 42 24740185
2004 Non-self-discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients. International journal of cancer 41 15252841
2020 CSPG4-Specific CAR.CIK Lymphocytes as a Novel Therapy for the Treatment of Multiple Soft-Tissue Sarcoma Histotypes. Clinical cancer research : an official journal of the American Association for Cancer Research 37 32900797
2016 Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype. Cell reports 37 27425618
2011 The CSPG4-specific monoclonal antibody enhances and prolongs the effects of the BRAF inhibitor in melanoma cells. Immunologic research 34 21717063
2016 A novel approach for targeted elimination of CSPG4-positive triple-negative breast cancer cells using a MAP tau-based fusion protein. International journal of cancer 32 27037627
2019 Arming T Cells with a gp100-Specific TCR and a CSPG4-Specific CAR Using Combined DNA- and RNA-Based Receptor Transfer. Cancers 30 31137488
1989 Cell surface molecules of human melanoma. Immunohistochemical analysis of the gp57, GD3, and mel-CSPG antigenic systems. The American journal of pathology 30 2916650
2005 Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody. International journal of cancer 29 15578703
2018 Cell surface chondroitin sulphate proteoglycan 4 (CSPG4) binds to the basement membrane heparan sulphate proteoglycan, perlecan, and is involved in cell adhesion. Journal of biochemistry 28 29462330
2020 A Novel Antibody-Drug Conjugate (ADC) Delivering a DNA Mono-Alkylating Payload to Chondroitin Sulfate Proteoglycan (CSPG4)-Expressing Melanoma. Cancers 27 32331483
2013 Diversified expression of NG2/CSPG4 isoforms in glioblastoma and human foetal brain identifies pericyte subsets. PloS one 27 24386429
2018 Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 25 29565434
2021 Difference in outcome between curative intent vs marginal excision as a first treatment in dogs with oral malignant melanoma and the impact of adjuvant CSPG4-DNA electrovaccination: A retrospective study on 155 cases. Veterinary and comparative oncology 24 33751759
2019 Identification of CSPG4 as a promising target for translational combinatorial approaches in osteosarcoma. Therapeutic advances in medical oncology 24 31217827
2014 Chondroitin sulfate proteoglycan CSPG4 as a novel hypoxia-sensitive marker in pancreatic tumors. PloS one 24 24932730
2019 Furanodienone overcomes temozolomide resistance in glioblastoma through the downregulation of CSPG4-Akt-ERK signalling by inhibiting EGR1-dependent transcription. Phytotherapy research : PTR 23 31006910
2021 Myelin Debris Stimulates NG2/CSPG4 Expression in Bone Marrow-Derived Macrophages in the Injured Spinal Cord. Frontiers in cellular neuroscience 22 33815067
2013 The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function. Placenta 22 23953863
2017 Effects of chondroitin sulfate proteoglycan 4 (NG2/CSPG4) on soft-tissue sarcoma growth depend on tumor developmental stage. The Journal of biological chemistry 21 29196603
2014 A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues. Cancer letters 21 25016058
2018 Proximity Labeling by a Recombinant APEX2-FGF1 Fusion Protein Reveals Interaction of FGF1 with the Proteoglycans CD44 and CSPG4. Biochemistry 20 29812912
2017 CSPG4: A Target for Selective Delivery of Human Cytolytic Fusion Proteins and TRAIL. Biomedicines 20 28657611
2003 Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi. American journal of clinical pathology 20 12710131
2025 Human CSPG4-targeting CAR-macrophages inhibit melanoma growth. Oncogene 19 40082557
2020 In vivo safety profile of a CSPG4-directed IgE antibody in an immunocompetent rat model. mAbs 19 31769737
2019 CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. International journal of molecular sciences 19 31195686
2018 NG2 expression in NG2 glia is regulated by binding of SoxE and bHLH transcription factors to a Cspg4 intronic enhancer. Glia 19 30306660
2022 Decitabine-Mediated Upregulation of CSPG4 in Ovarian Carcinoma Cells Enables Targeting by CSPG4-Specific CAR-T Cells. Cancers 18 36291817
2020 Targeting CSPG4 for isolation of melanoma cell-derived exosomes from body fluids. HNO 17 32006045
2023 A chimeric human/dog-DNA vaccine against CSPG4 induces immunity with therapeutic potential in comparative preclinical models of osteosarcoma. Molecular therapy : the journal of the American Society of Gene Therapy 16 37312451
2021 CSPG4 Is a Potential Therapeutic Target in Anaplastic Thyroid Cancer. Thyroid : official journal of the American Thyroid Association 16 34078123
2022 Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial. Journal for immunotherapy of cancer 15 35580930
2021 Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF. Oncology reports 15 33649790
2023 Cspg4 microglia contribute to microgliosis during neurodegeneration. Proceedings of the National Academy of Sciences of the United States of America 14 36795751
2021 Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia. Cancers 14 34638301
2016 Functional roles of CSPG4/NG2 in chondrosarcoma. International journal of experimental pathology 13 27292772
2014 Detection of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma. Methods in molecular biology (Clifton, N.J.) 13 24258997
2022 NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis. Frontiers in dental medicine 12 36685663
2021 NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells. Scientific reports 12 33727640
2021 Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism. Redox biology 12 34952462
2023 CSPG4 as a target for the specific killing of triple-negative breast cancer cells by a recombinant SNAP-tag-based antibody-auristatin F drug conjugate. Journal of cancer research and clinical oncology 11 37432459
2022 A Linarin Derivative Protects against Ischemia-Induced Neuronal Injury in Mice by Promoting Cerebral Blood Flow Recovery via KDELR-Dependent CSPG4 Activation. Oxidative medicine and cellular longevity 11 35927993
2025 B7-H3 and CSPG4 co-targeting as Pan-CAR-T cell treatment of triple-negative breast cancer. Journal for immunotherapy of cancer 9 40425233
2024 Chondroitin sulfate modification of CSPG4 regulates the maintenance and differentiation of glioma-initiating cells via integrin-associated signaling. The Journal of biological chemistry 9 38309500
2024 Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma. Cancers 9 39409881
2023 Nectin-3 and shed forms of CSPG4 can serve as epithelial cell receptors for Clostridioides difficile TcdB. mBio 9 37747247
2023 Combining CSPG4-CAR and CD20-CCR for treatment of metastatic melanoma. Frontiers in immunology 9 37901209
2023 CSPG4 CAR-redirected Cytokine Induced Killer lymphocytes (CIK) as effective cellular immunotherapy for HLA class I defective melanoma. Journal of experimental & clinical cancer research : CR 8 37993874
2015 Chondroitin sulfate proteoglycan-4 (CSPG4)-specific monoclonal antibody 225.28 in detection of acute myeloid leukemia blasts. Oncology research 8 25706398
2011 Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA) antibodies does not ensure biological activity. PloS one 8 21573118
2020 Chondroitin Sulphate Proteoglycan 4 (NG2/CSPG4) Localization in Low- and High-Grade Gliomas. Cells 7 32599896
2005 Cross-reactivity of mimotopes with a monoclonal antibody against the high molecular weight melanoma-associated antigen (HMW-MAA) does not predict cross-reactive immunogenicity. Melanoma research 7 15846144
2023 Trophoblast-specific knockdown of CSPG4 expression causes pregnancy complications with poor placentation in mice. Reproductive biology 6 36634519
2022 Immunotherapeutic Targeting of NG2/CSPG4 in Solid Organ Cancers. Vaccines 6 35891187
2021 The Function of NG2/CSPG4-expressing Cells in the Rat Spinal Cord Injury: An Immunoelectron Microscopy Study. Neuroscience 6 34102261
2025 Targeting CSPG4 enhances the anti-tumor activity of CAR-NK cells for glioblastoma. Cellular oncology (Dordrecht, Netherlands) 5 40720084
2023 Discovery of Hippo signaling as a regulator of CSPG4 expression and as a therapeutic target for Clostridioides difficile disease. PLoS pathogens 5 36972308
2018 Effect of TGFβ1 and nAG on Astrocyte Cultures: A Study of Astrocyte Proliferation and the Expression of GFAP, CSPG4, S100B and IL-6. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 5 30501829
2024 Identification of CSPG4 as a Biomarker and Therapeutic Target for Infantile Post-Hemorrhagic Hydrocephalus via Multi-Omics Analysis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 4 39686677
2025 B7-H3 and CSPG4-targeted CAR T cells as potent effectors in anaplastic thyroid cancer. Journal of experimental & clinical cancer research : CR 3 40847369
2024 CSPG4-targeting CAR-macrophages inhibit melanoma growth. bioRxiv : the preprint server for biology 3 38895447
2023 VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen. International journal of molecular sciences 3 36768830
2023 Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors. Frontiers in immunology 3 37849763
2018 CSPG4 Shows Promise for Glioblastoma CAR T Therapy. Cancer discovery 3 29540359
2025 CSPG4 overexpression implicates higher risks of recurrence and tumorigenesis after surgical intervention of vocal fold Leukoplakia. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 2 39863819
2025 Clinical evaluation of HuDo-CSPG4 DNA electroporation as adjuvant treatment for canine oral malignant melanoma: comparison of two vaccination protocols. The veterinary quarterly 2 40059815
2025 Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through PIEZO1. bioRxiv : the preprint server for biology 2 40791371
2024 Cspg4 sculpts oligodendrocyte precursor cell morphology. Differentiation; research in biological diversity 2 39566199
2021 Identification of a germline CSPG4 variation in a family with neurofibromatosis type 1-like phenotype. Cell death & disease 2 34344877
2016 Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes. Experimental cell research 2 28011196
2025 CSPG4 involvement in endometrial decidualization contributes to the pathogenesis of preeclampsia†. Biology of reproduction 1 39563514
2025 Enhanced diagnostic potential of CSPG4 in melanoma and nevi: a comparative study with PRAME, CDC7 and Ki67. The Journal of pathology 1 40700516
2025 Possible Involvement of CSPG4 in Promoting Endothelial Cell Migration and Contributing to Angiogenesis during Skeletal Muscle Regeneration and Development in the Rat. Animal science journal = Nihon chikusan Gakkaiho 1 40769519
2024 CSPG4-dependent cytotoxicity for C. difficile TcdB is influenced by extracellular calcium and chondroitin sulfate. mSphere 1 38470254
2024 Cspg4 sculpts oligodendrocyte precursor cell morphology. bioRxiv : the preprint server for biology 1 39149260
2025 CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy. International journal of molecular sciences 0 40724839

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