Podoplanin: An emerging cancer biomarker and therapeutic target

Abstract

Podoplanin (PDPN) is a transmembrane receptor glycoprotein that is upregulated on transformed cells, cancer associated fibroblasts and inflammatory macrophages that contribute to cancer progression. In particular, PDPN increases tumor cell clonal capacity, epithelial mesenchymal transition, migration, invasion, metastasis and inflammation. Antibodies, CAR‐T cells, biologics and synthetic compounds that target PDPN can inhibit cancer progression and septic inflammation in preclinical models. This review describes recent advances in how PDPN may be used as a biomarker and therapeutic target for many types of cancer, including glioma, squamous cell carcinoma, mesothelioma and melanoma.

Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivity

“…Specifically, CEBPE is an established, myeloid-specific isoform and a critical factor for immature myeloid precursor differentiation (Akagi et al, 2010; Bedi et al, 2008; Rodriguez-Barrueco et al, 2015); TNFRSF1A, a prototypical TNF-alpha receptor, and TNF-alpha represent a critical checkpoint in MDSCs generation (Raveney et al, 2010; Sade-Feldman et al, 2013; Zhao et al, 2012); CD44 , a maker of normal myelopoeisis and acute myeloid leukemia (Charrad et al, 1999; Jin et al, 2006) is expressed in mesenchymal-like GBM cells (Johansson et al, 2017; Mooney et al, 2016); CXCL14, is also an established MDSC marker (Shurin et al, 2005). Independently, aberrant activation of PDPN, LGALS1, and CDKN1A is consistent with the invasive phenotype presented by these cells (Ilarregui et al, 2009; Krishnan et al, 2018; Okuma et al, 2017; Shiina et al, 2016). RCAN1 is a critical regulator of the calcineurin-NFAT pathway in MDSCs, whose activity is mimicked by the classic immunosuppressive drug cyclosporine A that promotes MDSCs recruitment (Crabtree, 2001; Crabtree and Schreiber, 2009; Wang et al, 2015; Yang et al, 2018a).…”

Functional significance of the platelet immune receptors GPVI and CLEC-2

“…Cytokines induce podoplanin expression, which in some cases leads to further cytokine production as well as metalloproteinase expression, facilitating tumor cell invasion. In mouse models, podoplanin promotes tumor growth, epithelial-mesenchymal transition (EMT), invasion, and metastasis (50,139,142). Many of these actions are mediated through platelet CLEC-2, including tumor progression, metastasis, and cancer-induced thrombosis (143)(144)(145)(146).…”

Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma

“…First, MPM cells with no or low podoplanin expression, such as H28 and MSTO‐211H, were not captured with the CTC‐chip conjugated with the antipodoplanin Ab, as expected (Figure ). Podoplanin is a transmembrane receptor glycoprotein that is highly expressed on cells of mesothelial origin . The majority (90%‐100%) of mesotheliomas show positive staining of podoplanin and it is a most useful marker for the pathological diagnosis .…”

“…Podoplanin is a transmembrane receptor glycoprotein that is highly expressed on cells of mesothelial origin. 17 The majority (90%-100%) of mesotheliomas show positive staining of podoplanin and it is a most useful marker for the pathological diagnosis. 18 However, Ordóñez reported that podoplanin expres- to 96 hours at room temperature.…”