Podoplanin (PDPN) (PDPN)

Podoplanin (PDPN) is a type I transmembrane sialoglycoprotein that is highly expressed in various cancers, including glioblastoma, mesothelioma, and squamous cell carcinoma (UniProt Q86YL7). In malignant cells, PDPN often undergoes aberrant O-glycosylation, leading to the formation of tumor-associated epitopes such as the Tn antigen, which are largely absent in normal tissues (Kato et al., Sci Rep, 2016). This aberrantly glycosylated PDPN promotes tumor progression and metastasis by binding to the CLEC-2 receptor on platelets, triggering platelet aggregation and helping tumor cells evade the immune system (Fujita & Takagi, Cancer Sci, 2012). Because normal PDPN expression is found in critical tissues like the lung and kidney, therapeutic development focuses on antibodies like LpMab-2 and LpMab-23 that specifically recognize these cancer-associated glyco-epitopes to minimize off-target effects (Shiina et al., Oncotarget, 2016). These targeted therapies, including monoclonal antibodies and CAR-T cells, aim to induce antibody-dependent cellular cytotoxicity (ADCC) or direct cell lysis while sparing healthy cells (Kaneko et al., Gene, 2017).

Other names

AggrusT1-alphagp36PA2.26 antigenOTS8Glycoprotein 36Cancer-specific podoplaninTn-podoplanin

Therapeutic agents target the aberrantly glycosylated epitope of Podoplanin to inhibit its interaction with the CLEC-2 receptor on platelets, thereby preventing tumor-induced platelet aggregation and metastasis (Fujita & Takagi, Cancer Sci, 2012). Monoclonal antibodies such as LpMab-23 also mediate tumor cell destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Kato et al., Sci Rep, 2016). Additionally, chimeric antigen receptor (CAR) T-cell therapies are being developed to recognize these specific glyco-epitopes for direct cytotoxic elimination of PDPN-positive malignant cells (Shiina et al., Oncotarget, 2016).