Abstract
Podoplanin (PDPN) is a well-conserved, mucin-type transmembrane protein expressed in multiple tissues during ontogeny and in adult animals, including the brain, heart, kidney, lungs, osteoblasts, and lymphoid organs. Studies of PDPN-deficient mice have demonstrated that this molecule plays a critical role in development of the heart, lungs, and lymphatic system. PDPN is widely used as a marker for lymphatic endothelial cells and fibroblastic reticular cells of lymphoid organs and for lymphatics in the skin and tumor microenvironment. Much of the mechanistic insight into PDPN biology has been gleaned from studies of tumor cells; tumor cells often upregulate PDPN as they undergo epithelial-mesenchymal transition and this upregulation is correlated with increased motility and metastasis. The physiological role of PDPN that has been most studied is its ability to aggregate and activate CLEC-2-expressing platelets, as PDPN is the only known endogenous ligand for CLEC-2. However, more recent studies have revealed that PDPN also plays crucial roles in the biology of immune cells, including T cells and dendritic cells. This review will provide a comprehensive overview of the diverse roles of PDPN in development, immunology, and cancer.
Highlights
Podoplanin (PDPN) is a 36- to 43-kDa mucin-type transmembrane protein
PDPN was first described on lymphatic endothelial cells (LECs) as the E11 antigen (Wetterwald et al, 1996) and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38 (Farr et al, 1992a,b; Table 1)
PDPN is homologous to T1a/rTI40, one of the first molecular markers of alveolar type I epithelial cells (Rishi et al, 1995; Williams et al, 1996; Table 1), PA2.26, which is upregulated in skin keratinocytes upon injury (Scholl et al, 1999), OTS-8, a molecule induced in osteoblasts upon phorbol ester treatment (Nose et al, 1990), and Aggrus, a platelet-aggregating factor (Kato et al, 2003)
Summary
Podoplanin (PDPN) is a 36- to 43-kDa mucin-type transmembrane protein. It has homologues in humans, mice, rats, dogs, and hamsters and is relatively well conserved between species. PDPN is homologous to T1a/rTI40, one of the first molecular markers of alveolar type I epithelial cells (Rishi et al, 1995; Williams et al, 1996; Table 1), PA2.26, which is upregulated in skin keratinocytes upon injury (Scholl et al, 1999), OTS-8, a molecule induced in osteoblasts upon phorbol ester treatment (Nose et al, 1990), and Aggrus, a platelet-aggregating factor (Kato et al, 2003) This molecule was given the name podoplanin due to its expression on kidney podocytes and possible involvement in the flattening of podocyte foot processes (Breiteneder-Geleff et al, 1997). PDPN expression is increasingly restricted such that in an adult animal, PDPN is predominantly www.frontiersin.org
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