Aberrantly O-glycosylated podoplanin (PDPN) (PDPN)

Aberrantly O-glycosylated podoplanin is a tumor-specific variant of podoplanin (PDPN), a type I transmembrane sialoglycoprotein. In healthy tissues, PDPN is expressed in lymphatic endothelial cells, renal podocytes, and lung type I alveolar cells, where it maintains vascular integrity and lymphatic development (UniProt Q86YL7). However, in many cancers such as glioblastoma and squamous cell carcinoma, PDPN undergoes aberrant O-glycosylation, often characterized by the presence of truncated glycans like the Tn antigen (GalNAc-Ser/Thr). This specific glycoform acts as a potent inducer of platelet aggregation by binding to the C-type lectin-like receptor 2 (CLEC-2) on platelets, a process that facilitates tumor cell survival in the bloodstream and promotes hematogenous metastasis (PubMed: 24583056). Therapeutic targeting of this molecule utilizes "Cancer-specific Monoclonal Antibodies" (CasMabs), such as LpMab-2, which are engineered to recognize the unique glycopeptide epitope found only on malignant cells (PubMed: 27107430). These drugs aim to provide high anti-tumor efficacy through immune-mediated cell killing while minimizing the risk of side effects associated with targeting normal PDPN-expressing tissues.

Other names

PodoplaninAggrusT1-alphagp36PA2.26 antigenCancer-specific podoplaninGlycoprotein 36

Selective binding to cancer-specific glycoepitopes (e.g., Tn antigen on Thr52) to induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), or blocking the PDPN-CLEC-2 interaction to inhibit tumor-induced platelet aggregation and metastasis (PubMed: 27107430, 24583056).