Affinage

PDPN

Podoplanin · UniProt Q86YL7

Length
162 aa
Mass
16.7 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDPN (podoplanin/Aggrus/PA2.26/E11/gp38) is a mucin-type transmembrane sialoglycoprotein that drives cell migration, tumor invasion, and hematogenous metastasis while also serving differentiated tissue functions such as mechanically stimulated osteocyte dendrite formation (PMID:10574709, PMID:14522983, PMID:16738320). At the cell surface, PDPN couples to the actin cytoskeleton by associating with ERM proteins ezrin and moesin, redistributing ezrin to membrane projections, remodeling cortical actin, destabilizing E-/P-cadherin adherens junctions, and converting epithelial cells to a motile, fibroblastoid, metastatic phenotype (PMID:10574709, PMID:11092535, PMID:15515019); in carcinoma cells it regulates ERM phosphorylation together with MMP-2/MMP-9 activity to promote invadopodia-driven matrix degradation and invasion (PMID:30654768). Its prometastatic activity depends on a conserved extracellular PLAG domain carrying sialylated core-1 O-glycans on Thr34/Thr52, which directly engages the platelet receptor CLEC-2 to trigger platelet aggregation, tumor cell coating, microvascular arrest, and platelet-induced tumor proliferation (PMID:14522983, PMID:15231832, PMID:16766141, PMID:17392172, PMID:23991201). PDPN cytoplasmic function is controlled by phosphorylation of two conserved intracellular serines by PKA and CDK5, which cooperatively suppress motility (PMID:23530051, PMID:25959509). PDPN abundance and signaling are further tuned post-transcriptionally and post-translationally by IMP-3 (IGF2BP3)-mediated mRNA stabilization, calpain-1 proteolysis, inhibitory complex formation with the tetraspanin CD9, and antagonism by CD177 (PMID:19146981, PMID:22859271, PMID:18541721, PMID:34879110). In the tumor stroma, PDPN+ cancer-associated fibroblasts sustain a pro-angiogenic CCL2/STAT3 feedback program (PMID:39115624).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established that PDPN is not a passive surface marker but a cytoskeletal organizer, linking it physically to ERM proteins and to actin-based motility.

    Evidence Reciprocal Co-IP, confocal/immunoelectron microscopy, and ectopic expression in keratinocytes

    PMID:10574709

    Open questions at the time
    • Did not define the ERM-binding motif on PDPN
    • Did not link ERM engagement to in vivo phenotypes
  2. 2000 High

    Showed that PDPN expression alone confers a transformed, lymphatically invasive, metastatic phenotype via adherens junction destabilization.

    Evidence Stable transfection, Western blot, immunofluorescence, and xenograft transplantation in nude mice

    PMID:11092535

    Open questions at the time
    • Mechanism of cadherin proteolytic degradation not identified
    • Surface receptor mediating metastasis not yet known
  3. 2003 High

    Defined the platelet aggregation-stimulating (PLAG) domain as the functional determinant of PDPN-induced platelet aggregation, independent of plasma factors.

    Evidence Protein purification, platelet aggregation assay, neutralizing antibody (8F11), and CHO expression

    PMID:14522983

    Open questions at the time
    • Platelet receptor not identified
    • Specific glycan requirement not yet resolved
  4. 2004 High

    Resolved the glycan code for activity, showing sialylated core-1 O-glycans (not N-glycans) are required for platelet aggregation.

    Evidence Expression in glycosylation-deficient CHO mutants (Lec1/Lec2/Lec8) with platelet aggregation and lectin blotting

    PMID:15231832

    Open questions at the time
    • Did not map which threonines carry the critical glycans
    • Glycosyltransferases responsible not identified
  5. 2006 High

    Mapped PLAG-domain architecture, showing tandem repeats with the first or last (not middle) repeat critical for platelet aggregation.

    Evidence cDNA cloning across mammals, site-directed mutagenesis, and platelet aggregation assays

    PMID:16766141

    Open questions at the time
    • Single critical threonine residues not yet pinpointed
    • Structural basis of repeat redundancy unknown
  6. 2006 High

    Extended PDPN function beyond cancer, establishing it as required for mechanically stimulated osteocyte dendrite elongation.

    Evidence siRNA knockdown in MLO-Y4 cells, fluid flow shear stress, and in vivo mechanical loading

    PMID:16738320

    Open questions at the time
    • Signaling pathway downstream of shear stress to PDPN not defined
    • Whether ERM/CLEC-2 axes operate in osteocytes unknown
  7. 2007 High

    Tied platelet aggregation mechanistically to metastasis, identifying Thr34/Thr52 as the critical glycosylated residues and showing aspirin reduces metastasis.

    Evidence In vivo metastasis models, Thr34/Thr52 point mutagenesis, platelet aggregation assays, and drug treatment

    PMID:17392172

    Open questions at the time
    • Platelet receptor still unidentified at this stage
    • Contribution of non-platelet mechanisms to metastasis not separated
  8. 2008 High

    Identified CD9 as a negative regulator forming a TM1/TM2-dependent complex that suppresses PDPN-driven platelet aggregation and metastasis.

    Evidence Co-IP with domain deletion mutagenesis, membrane fractionation, and in vitro/in vivo assays

    PMID:18541721

    Open questions at the time
    • Mechanism by which CD9 sterically blocks CLEC-2 engagement not resolved
    • Physiological contexts of CD9-PDPN balance unclear
  9. 2008 High

    Established that PDPN protein levels are set post-translationally, with calpain-1 cleaving PDPN to limit surface abundance.

    Evidence In vitro calpain cleavage assay, calpeptin vs lactacystin pharmacology, and Western blot

    PMID:19146981

    Open questions at the time
    • Cleavage site on PDPN not mapped
    • Physiological trigger for calpain processing unknown
  10. 2012 Medium

    Revealed post-transcriptional control of PDPN by IMP-3 (IGF2BP3), linking mRNA stability to invadopodia-mediated matrix degradation.

    Evidence siRNA knockdown, 3'UTR ISH and luciferase reporter, and xenograft model

    PMID:22859271

    Open questions at the time
    • Direct IMP-3 binding site on the 3'UTR not finely mapped
    • Single-lab study
  11. 2013 High

    Closed the long-standing gap by identifying CLEC-2 as the direct platelet receptor for PDPN and connecting it to platelet-induced tumor proliferation.

    Evidence Direct binding assay, neutralizing antibody MS-1, siRNA knockdown, and in vivo xenograft/metastasis models

    PMID:23991201

    Open questions at the time
    • Structural stoichiometry of PDPN-CLEC-2 not defined here
    • Relative weight of proliferation vs aggregation in vivo unclear
  12. 2013 High

    Defined intracellular regulation of PDPN motility function, showing PKA phosphorylation of two conserved serines suppresses migration.

    Evidence Pdpn-null MEFs, Ser→Ala/Asp mutagenesis, PKA kinase assay, and migration/co-culture assays

    PMID:23530051

    Open questions at the time
    • How serine phosphorylation alters ERM coupling not resolved
    • Upstream signals activating PKA toward PDPN unknown
  13. 2014 Medium

    Generalized PDPN-CLEC-2 signaling to inflammatory stroma, showing synovial fibroblast PDPN drives platelet-induced IL-6/IL-8 without affecting migration.

    Evidence gp38 siRNA silencing in synovial fibroblasts, platelet co-culture, and gene expression analysis

    PMID:24932813

    Open questions at the time
    • Signaling pathway from PDPN-platelet contact to cytokine induction not mapped
    • Negative migration result limits generalization
  14. 2015 High

    Refined the kinase control of PDPN by identifying CDK5 as a second kinase cooperating with PKA on both serines to suppress motility.

    Evidence In vitro PKA and CDK5 kinase assays with single-residue mutagenesis and motility assays

    PMID:25959509

    Open questions at the time
    • Spatiotemporal coordination of the two kinases in cells not defined
    • Phosphatase counteracting these sites unknown
  15. 2019 Medium

    Linked PDPN to upstream MAPK signaling and downstream MMP activity in thyroid carcinoma invasion through ERM phosphorylation control.

    Evidence siRNA knockdown, invasion assays, zymography, and MAPK inhibitors (U0126, PLX4720)

    PMID:30654768

    Open questions at the time
    • Direct mechanism connecting PDPN to MMP transcription unclear
    • Single-lab, single-cell-line study
  16. 2021 Medium

    Identified CD177 as a novel surface binding partner acting as a functional antagonist of PDPN on cancer-associated fibroblasts.

    Evidence High-throughput surface interactome screen, quantitative phosphoproteomics, and functional CAF assays

    PMID:34879110

    Open questions at the time
    • Mechanism of CD177 antagonism not resolved
    • Interaction not validated by reciprocal structural/biochemical means
  17. 2024 Medium

    Showed PDPN+ CAFs drive tumor angiogenesis via an autocrine PDPN/CCL2/STAT3 feedback loop signaling to endothelial cells through ACKR1.

    Evidence Single-cell analysis, p65 ChIP on CCL2 promoter, CCL2 neutralization, and in vivo tumor assays

    PMID:39115624

    Open questions at the time
    • How PDPN initiates the p65/CCL2 program mechanistically not defined
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of the PDPN-CLEC-2 interface, how intracellular serine phosphorylation reprograms ERM coupling, and how the competing regulators (CD9, CD177, calpain-1, IMP-3) are integrated in vivo remain unresolved.
  • No high-resolution structure of full-length PDPN or its receptor complexes
  • Integration of post-transcriptional, proteolytic, and phosphorylation controls into a single regulatory model is undefined
  • Tissue-specific roles (osteocyte vs tumor vs synovial) not mechanistically unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0048018 receptor ligand activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CAPN1CD177CD9CDK5CLEC-2EZRIGF2BP3MSN

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 PA2.26 (PDPN) is a mucin-like transmembrane glycoprotein that colocalizes with ERM (ezrin, radixin, moesin) family proteins in actin-rich microvilli and plasma membrane projections; ezrin and moesin (but not radixin) can be co-immunoprecipitated with PA2.26. Ectopic expression of PA2.26 in nontumorigenic keratinocytes induces epithelial-fibroblastoid morphological conversion with increased plasma membrane extensions, major reorganization of the actin cytoskeleton, redistribution of ezrin to cell-surface projections, and enhanced motility. Co-immunoprecipitation, confocal/immunoelectron microscopy, ectopic expression in keratinocytes with functional readouts Journal of cell science High 10574709
2000 Ectopic expression of PA2.26 (PDPN) in premalignant MCA3D keratinocytes leads to destabilization of adherens junctions (downregulation of E- and P-cadherin protein via proteolytic degradation), loss of cortical actin, vimentin/K8 upregulation, K14 downregulation, and acquisition of a fully transformed, metastatic phenotype including lymphatic invasion and regional lymph node metastases in nude mice. Stable transfection, Western blot, immunofluorescence, xenograft tumor transplantation Laboratory investigation High 11092535
2003 Aggrus/PDPN (T1alpha) directly induces platelet aggregation without requiring plasma components. The platelet aggregation-stimulating (PLAG) domain bearing putative O-glycosylated threonine residues is the critical determinant; an 8F11 neutralizing monoclonal antibody targeting this domain suppresses tumor-induced platelet aggregation. Protein purification, platelet aggregation assay, monoclonal antibody neutralization, expression in CHO cells The Journal of biological chemistry High 14522983
2004 Sialylated O-glycans (specifically sialylated core 1 structures: sialic acid plus Galβ1,3GalNAc-Ser/Thr) on Aggrus/PDPN are critical for its platelet aggregation-inducing activity. Expression in CMP-sialic acid transporter-deficient (Lec2) or UDP-galactose transporter-deficient (Lec8) CHO cells abolished platelet aggregation, while N-glycan-deficient (Lec1) cells retained activity. Stable expression in glycosylation-deficient CHO cell mutants, platelet aggregation assay, lectin blotting The Journal of biological chemistry High 15231832
2005 Human PA2.26/PDPN colocalizes with ezrin at the cell surface in oral squamous cell carcinoma cells. Ectopic expression in HeLa and HaCaT cells promotes redistribution of ezrin to cell edges, formation of cell-surface protrusions, and reduced Ca2+-dependent cell-cell adhesiveness. Double immunofluorescence, confocal microscopy, ectopic expression with functional assays International journal of cancer Medium 15515019
2006 The PLAG domain of Aggrus/PDPN is conserved across mammalian homologues (rat, hamster, dog, bovine, human, mouse) and contains three tandem repeats. Point mutation shows that either the first or last (but not the middle) PLAG domain is critical for platelet aggregation-inducing activity. Bovine Aggrus with a sporadic deletion in the first PLAG domain lacks platelet aggregation activity. cDNA cloning, site-directed mutagenesis, platelet aggregation assay, sequence analysis Gene High 16766141
2006 E11/gp38 (PDPN) is the earliest osteocyte-selective protein expressed during osteoblast-to-osteocyte differentiation. Fluid flow shear stress increases E11 mRNA in osteocyte-like MLO-Y4 cells. siRNA knockdown of E11 blocks shear-stress-induced dendrite elongation in MLO-Y4 cells. Mechanical load in vivo increases E11 expression in osteocytes. These results establish E11/gp38 as functionally required for mechanically-stimulated osteocyte dendrite elongation. siRNA knockdown, fluid flow shear stress assay, in vivo mechanical loading, immunostaining, RT-PCR Molecular and cellular biology High 16738320
2007 Aggrus/podoplanin promotes pulmonary metastasis by inducing platelet aggregation. CHO cells expressing Aggrus show platelet coating and lung microvasculature arrest within 30 minutes of injection. Point mutations at Thr34 and Thr52 in the PLAG domain abolish both platelet aggregation and metastasis. Aspirin treatment reduces metastatic foci. In vivo experimental and spontaneous metastasis mouse models, point mutagenesis (Thr34/Thr52), platelet aggregation assay, drug treatment The American journal of pathology High 17392172
2008 CD9 (tetraspanin) forms a complex with Aggrus/podoplanin via its transmembrane domains 1 and 2 (TM1 and TM2). CD9 and Aggrus colocalize in low-density membrane fractions. CD9 expression inhibits Aggrus-induced platelet aggregation and pulmonary metastasis; deletion of TM1 and TM2 abolishes this inhibition and also disrupts CD9 homophilic interaction and low-density membrane localization. Co-immunoprecipitation, domain deletion mutagenesis, platelet aggregation assay, in vivo metastasis assay, membrane fractionation Blood High 18541721
2008 Podoplanin/PA2.26 protein levels are regulated post-translationally by calpain-mediated proteolysis. Calpain-1 cleaves podoplanin in vitro; treatment with calpain inhibitor calpeptin (but not the proteasome inhibitor lactacystin) causes podoplanin accumulation in multiple tumor cell lines that transcribe PDPN but show little protein. In vitro calpain cleavage assay, pharmacological inhibition (calpeptin vs lactacystin), Western blot The international journal of biochemistry & cell biology High 19146981
2012 IMP-3 (IGF2BP3) stabilizes the PDPN mRNA via interaction with the 3'UTR, maintaining PDPN expression required for functional invadopodia formation and extracellular matrix degradation in oral squamous cell carcinoma cells. IMP-3 depletion reduces PDPN mRNA levels and abolishes ECM degradation activity despite intact invadopodia structure. siRNA knockdown, RNA in situ hybridization with 3'UTR probe, luciferase reporter assay with PDPN 3'UTR, xenograft model Carcinogenesis Medium 22859271
2013 Aggrus/podoplanin directly binds to the platelet receptor CLEC-2, and this interaction mediates platelet aggregation, platelet-induced tumor cell proliferation, and pulmonary metastasis. Anti-Aggrus antibody MS-1 blocks Aggrus-CLEC-2 binding and suppresses both metastasis and tumor growth in vivo. Aggrus knockdown reduces platelet-induced proliferation in vitro. Binding assay (Aggrus-CLEC-2), anti-Aggrus neutralizing monoclonal antibody, siRNA knockdown, in vivo xenograft/metastasis models PloS one High 23991201
2013 The two conserved intracellular serine residues of PDPN can be phosphorylated by PKA (protein kinase A). Conversion of these serines to non-phosphorylatable alanine enhances cell migration, while conversion to phosphomimetic aspartate decreases cell migration. PDPN expression in fibroblasts facilitates motility and viability of co-cultured melanoma cells. Pdpn knockout mouse embryonic fibroblasts, site-directed mutagenesis (Ser→Ala and Ser→Asp), PKA phosphorylation assay, cell migration assays, co-culture The Journal of biological chemistry High 23530051
2014 Podoplanin (gp38) in rheumatoid arthritis synovial fibroblasts interacts with the platelet receptor CLEC-2 in vivo. gp38 silencing in synovial fibroblasts reduces IL-6 and IL-8 gene expression induced by fibroblast-platelet interaction, but does not affect fibroblast migration or invasion. gp38 siRNA silencing in cultured synovial fibroblasts, platelet-fibroblast co-culture, gene expression analysis, immunohistochemistry PloS one Medium 24932813
2015 Both PKA and CDK5 phosphorylate PDPN on its two conserved intracellular serine residues, and they cooperate to phosphorylate both residues to decrease cell motility. CDK5 was identified as a new PDPN kinase in addition to PKA. In vitro kinase assays with PKA and CDK5, site-directed mutagenesis of individual serine residues, cell motility assays Experimental cell research High 25959509
2019 PDPN promotes invasiveness in BcPAP papillary thyroid carcinoma cells by regulating ezrin/radixin/moesin (E/R/M) protein phosphorylation, MMP-2 and MMP-9 expression/activity, actin cytoskeleton remodeling, and cellular protrusion formation. PDPN expression is associated with the MAPK signaling pathway; MAPK inhibition decreases PDPN expression, increases E/R/M phosphorylation, and reduces cell migration. siRNA knockdown, scratch/Transwell invasion assays, zymography, Western blot, MAPK pathway inhibitors (U0126, PLX4720) BMC cancer Medium 30654768
2021 CD177 (neutrophil protein) is a novel cell-surface binding partner of PDPN on cancer-associated fibroblasts, identified by high-throughput cell surface interactome screening. CD177 acts as a functional antagonist of PDPN, recapitulating the phenotype of PDPN-deficient CAFs. Quantitative phosphoproteomics of CAFs links PDPN to cell signaling, growth, and actomyosin contractility pathways. High-throughput cell surface protein interaction screen, quantitative phosphoproteomics, cellular functional assays PloS one Medium 34879110
2024 PDPN+ cancer-associated fibroblasts in colorectal cancer maintain CAF heterogeneity and promote angiogenesis via an autocrine PDPN/CCL2/STAT3 feedback loop. NF-κB p65 binds the CCL2 promoter to induce CCL2 secretion; paracrine CCL2 activates STAT3 in endothelial cells. CCL2 interacts with its non-classical receptor ACKR1 on endothelial cells to mediate pro-angiogenic effects. STAT3 inhibitor WP1066 blocks both the feedback loop in CAFs and STAT3 in endothelial cells. Single-cell analysis, ChIP/promoter binding assay (p65 on CCL2 promoter), CCL2 neutralizing antibody, AKT inhibitor, in vivo tumor growth assays Angiogenesis Medium 39115624

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer research 845 1596899
2002 Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 483 11950918
2020 Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4+ and PDPN+ CAFs to clinical outcome. Nature cancer 265 35122040
2005 Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology 247 15810951
2005 Characterization of human PA2.26 antigen (T1alpha-2, podoplanin), a small membrane mucin induced in oral squamous cell carcinomas. International journal of cancer 241 15515019
2003 Molecular identification of Aggrus/T1alpha as a platelet aggregation-inducing factor expressed in colorectal tumors. The Journal of biological chemistry 240 14522983
2006 E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation. Molecular and cellular biology 225 16738320
2005 Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 205 15389250
2005 D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Human pathology 192 15891998
2005 Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 192 16006773
2007 The platelet aggregation-inducing factor aggrus/podoplanin promotes pulmonary metastasis. The American journal of pathology 167 17392172
2013 Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2. PloS one 166 23991201
2004 Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors. Oncogene 134 15361850
1999 Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. Journal of cell science 127 10574709
2005 Alteration of tail fiber protein gp38 enables T2 phage to infect Escherichia coli O157:H7. Journal of biotechnology 115 15607229
2005 D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 114 15920541
2006 Conservation of a platelet activating domain of Aggrus/podoplanin as a platelet aggregation-inducing factor. Gene 111 16766141
2018 Peripheral PDGFRα+gp38+ mesenchymal cells support the differentiation of fetal liver-derived ILC2. The Journal of experimental medicine 100 29728440
2007 Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors. American journal of clinical pathology 97 17951199
2008 Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 90 18192971
2005 Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in early-stage squamous cell carcinoma of the uterine cervix. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 88 15467716
2004 Functional sialylated O-glycan to platelet aggregation on Aggrus (T1alpha/Podoplanin) molecules expressed in Chinese hamster ovary cells. The Journal of biological chemistry 84 15231832
1997 Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis. Molecular carcinogenesis 84 9328432
2006 Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours. Virchows Archiv : an international journal of pathology 81 16736189
2023 PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 80 36812747
2011 The gp38 adhesins of the T4 superfamily: a complex modular determinant of the phage's host specificity. Genome biology and evolution 78 21746838
2010 Value of p63 and podoplanin (D2-40) immunoreactivity in the distinction between primary cutaneous tumors and adenocarcinomas metastatic to the skin: a clinicopathologic and immunohistochemical study of 79 cases. Journal of cutaneous pathology 75 20377670
2010 The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 70 20190734
2023 A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability. Nature communications 68 37898647
2005 D2-40, a novel monoclonal antibody against the M2A antigen as a marker to distinguish hemangioblastomas from renal cell carcinomas. Acta neuropathologica 68 15864611
2007 D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 60 17277761
2008 Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis. Blood 55 18541721
2013 Serines in the intracellular tail of podoplanin (PDPN) regulate cell motility. The Journal of biological chemistry 52 23530051
2021 A CCHFV DNA vaccine protects against heterologous challenge and establishes GP38 as immunorelevant in mice. NPJ vaccines 50 33654101
2012 The impact of Aggrus/podoplanin on platelet aggregation and tumour metastasis. Journal of biochemistry 50 22992842
1994 Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis. Journal of virology 50 7933096
2012 Functional invadopodia formation through stabilization of the PDPN transcript by IMP-3 and cancer-stromal crosstalk for PDPN expression. Carcinogenesis 49 22859271
2011 Prevention of hematogenous metastasis by neutralizing mice and its chimeric anti-Aggrus/podoplanin antibodies. Cancer science 48 21824222
2009 Prox-1 and VEGFR3 antibodies are superior to D2-40 in identifying endothelial cells of lymphatic malformations--a proposal of a new immunohistochemical panel to differentiate lymphatic from other vascular malformations. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 46 18937526
1996 Local concentration of folate binding protein GP38 in sections of human ovarian carcinoma by in vitro quantitative autoradiography. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 45 8691264
2009 Podoplanin (D2-40) is a highly effective marker of follicular dendritic cells. Applied immunohistochemistry & molecular morphology : AIMM 44 18838918
2000 Ectopic expression of PA2.26 antigen in epidermal keratinocytes leads to destabilization of adherens junctions and malignant progression. Laboratory investigation; a journal of technical methods and pathology 44 11092535
2020 Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38. Journal of virology 43 31996434
2008 D2-40 expression by breast myoepithelium: potential pitfalls in distinguishing intralymphatic carcinoma from in situ carcinoma. Human pathology 43 18206495
2007 Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix. Gynecologic oncology 41 17604828
2008 Lymphatic invasion according to D2-40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus: algorithm for risk of nodal metastasis based on lymphatic invasion. Pathology international 40 18429826
2023 PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX. Cell death & disease 39 37993428
2008 Immunohistochemical demonstration of D2-40 in basal cell carcinomas of the skin. Journal of cutaneous pathology 39 18537863
2008 Podoplanin (d2-40): a new immunohistochemical marker for reactive follicular dendritic cells and follicular dendritic cell sarcomas. International journal of clinical and experimental pathology 39 18784810
2009 Prediction model of lymph node metastasis in superficial esophageal adenocarcinoma and squamous cell cancer including D2-40 immunostaining. Journal of surgical oncology 38 19548259
2006 D2-40: a reliable marker in the diagnosis of pleural mesothelioma. Pathobiology : journal of immunopathology, molecular and cellular biology 38 16785767
2010 The clinical significance of the tumor cell D2-40 immunoreactivity in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 37 20061046
2007 D2-40 expression demonstrates lymphatic vessel characteristics in the dural portion of the optic nerve sheath. Ophthalmic plastic and reconstructive surgery 37 17237687
2006 Lymphatic microvessel density using D2-40 is associated with nodal metastasis in non-small cell lung cancer. Oncology reports 37 16391866
2010 D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 36 20062007
2008 Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR-3. The American Journal of dermatopathology 36 18212541
2018 Peyer's patch myeloid cells infection by Listeria signals through gp38+ stromal cells and locks intestinal villus invasion. The Journal of experimental medicine 35 30355616
2014 Clinicopathological correlations of podoplanin (gp38) expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk. PloS one 35 24932813
2006 D2-40 is not a specific marker for cells of mesothelial origin in serous effusions. The American journal of surgical pathology 35 16819331
2006 The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement. Diagnostic cytopathology 34 17115439
2013 Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis. International journal of cancer 33 24222607
2006 Grading system of lymphatic invasion according to D2-40 immunostaining is useful for the prediction of nodal metastasis in squamous cell carcinoma of the uterine cervix. Histopathology 32 17064295
2014 Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma. Tumori 31 25343553
2019 Podoplanin (PDPN) affects the invasiveness of thyroid carcinoma cells by inducing ezrin, radixin and moesin (E/R/M) phosphorylation in association with matrix metalloproteinases. BMC cancer 29 30654768
2009 Embryonic stem cell transcription factors and D2-40 (podoplanin) as diagnostic immunohistochemical markers in ovarian germ cell tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 29 19483629
2010 Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver--re-evaluations of microlymphatic abnormalities. BMC gastroenterology 28 21059220
2012 Relationships between Lymph Node Metastasis and Expression of CD31, D2-40, and Vascular Endothelial Growth Factors A and C in Papillary Thyroid Cancer. Clinical and experimental otorhinolaryngology 27 22977712
2010 D2-40/podoplanin expression in the human placenta. Placenta 27 21095001
2006 D2-40 antibody immunoreactivity in developing human brain, brain tumors and cultured neural cells. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 16648867
2012 D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: a marker of metastatic risk. Journal of the American Academy of Dermatology 26 22521203
2011 Lymphatic tumor emboli detected by D2-40 immunostaining can more accurately predict lymph-node metastasis. World journal of surgery 26 21667194
2007 Diffuse membranous immunoreactivity for podoplanin (D2-40) distinguishes primary and metastatic seminomas from other germ cell tumors and metastatic neoplasms. American journal of clinical pathology 26 17951198
2017 Vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGFR-3 and D2-40 expressions in primary breast cancer: Association with lymph node metastasis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 25 28791841
2015 PKA and CDK5 can phosphorylate specific serines on the intracellular domain of podoplanin (PDPN) to inhibit cell motility. Experimental cell research 24 25959509
2008 Immunohistochemical expression of D2-40 in benign and malignant sebaceous tumors and comparison to basal and squamous cell carcinomas. The American Journal of dermatopathology 24 19033927
2008 Regulation of podoplanin/PA2.26 antigen expression in tumour cells. Involvement of calpain-mediated proteolysis. The international journal of biochemistry & cell biology 23 19146981
2013 Lymphatic Vessel Density and Vascular Endothelial Growth Factor Expression in Squamous Cell Carcinomas of Lip and Oral Cavity: A Clinicopathological Analysis with Immunohistochemistry Using Antibodies to D2-40, VEGF-C and VEGF-D. Yonago acta medica 22 24031149
2011 Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma. European journal of gynaecological oncology 22 22335030
2007 Diagnostic utility of D2-40 and podoplanin in effusion cell blocks. Diagnostic cytopathology 21 17497664
2024 PDPN/CCL2/STAT3 feedback loop alter CAF heterogeneity to promote angiogenesis in colorectal cancer. Angiogenesis 20 39115624
2014 Expression of the lymphatic marker podoplanin (D2-40) in human fetal eyes. Experimental eye research 20 25135789
2009 Immunostaining with D2-40 improves evaluation of lymphovascular invasion, but may not predict sentinel lymph node status in early breast cancer. BMC cancer 19 19356249
2016 Clinicopathological significance of lymphangiogenesis detected by immunohistochemistry using D2-40 monoclonal antibody in breast cancer. Fukushima journal of medical science 17 27210308
2010 Immunolabeling pattern of podoplanin (d2-40) may distinguish basal cell carcinomas from trichoepitheliomas: a clinicopathologic and immunohistochemical study of 49 cases. The American Journal of dermatopathology 17 20559122
2007 D2-40 is a sensitive and specific marker in differentiating primary adrenal cortical tumours from both metastatic clear cell renal cell carcinoma and phaeochromocytoma. Journal of clinical pathology 17 17660332
2007 Subepithelial extension of squamous cell carcinoma in the esophagus: histopathological study using D2-40 immunostaining for 108 superficial carcinomas. Pathology international 17 17988276
2022 PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma. Cancer gene therapy 16 36434176
2020 PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma. Cells 16 32380790
2014 Expression of Prox1, D2-40, and WT1 in spindle cell hemangioma. Journal of cutaneous pathology 16 24673328
2025 PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis. MedComm 15 39764562
2024 A novel PDPN antagonist peptide CY12-RP2 inhibits melanoma growth via Wnt/β-catenin and modulates the immune cells. Journal of experimental & clinical cancer research : CR 15 38167452
2012 Expressions of D2-40, CK19, galectin-3, VEGF and EGFR in papillary thyroid carcinoma. Gland surgery 15 25083424
2011 D2-40 immunoreactivity in penile squamous cell carcinoma: a marker of aggressiveness. Human pathology 15 21497368
2021 CD31 and D2-40 Contribute to Peritoneal Metastasis of Colorectal Cancer by Promoting Epithelial-Mesenchymal Transition. Gut and liver 14 32390409
2014 Clinical significance of detecting lymphatic and blood vessel invasion in stage II colon cancer using markers D2-40 and CD34 in combination. Asian Pacific journal of cancer prevention : APJCP 14 24606466
2021 The neutrophil protein CD177 is a novel PDPN receptor that regulates human cancer-associated fibroblast physiology. PloS one 13 34879110
2011 D2-40: an additional marker for myoepithelial cells of breast and the precaution in interpreting tumor lymphovascular invasion. International journal of clinical and experimental pathology 13 21326813
2025 Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread. Science translational medicine 12 39970234
2024 Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38. Cell reports 12 39002130
2014 Expression of p53, D2-40 and α-smooth muscle actin in different histological subtypes of facial basal cell carcinoma. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 12 24969973

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