Podoplanin

Podoplanin is a small mucin-type transmembrane glycoprotein encoded by the PDPN gene. It is a single-pass protein with a heavily O-glycosylated extracellular domain, a transmembrane segment, and a short cytoplasmic tail that binds ERM (ezrin/radixin/moesin) proteins to connect to the actin cytoskeleton. The extracellular region is rich in serine and threonine residues that carry extensive sugar chains, contributing to its mucin-like properties.

Expression of podoplanin is broad but characteristic. It is a marker of lymphatic endothelial cells and is widely used to distinguish lymphatic vessels from blood vessels. It is also expressed by mesothelial cells lining serous cavities, renal podocytes, and certain alveolar type I pneumocytes, as well as various other tissues and tumors. This pattern makes podoplanin a useful immunohistochemical marker in diagnostic pathology.

Functionally, podoplanin plays a crucial role in lymphangiogenesis and the separation of the lymphatic and blood vascular systems during development. It influences cell shape, motility, and adhesion through its interaction with the actin cytoskeleton via ERM proteins. Podoplanin can also induce platelet aggregation by binding to the platelet receptor CLEC-2, a mechanism that has implications for hemostasis, thrombosis, and, in cancer, tumor cell-induced platelets and metastasis.

Clinical significance includes its use as a diagnostic marker to identify lymphatic endothelium and lymphatic invasion by tumors. Overexpression or aberrant expression of podoplanin in certain cancers is associated with aggressive behavior and poorer prognosis, and it remains a target of research for therapies aimed at limiting metastasis and platelet activation.