Hypothetical molecular mechanisms by which podoplanin induces cancer-associated thrombosis. (A) Podoplanin expressed on the surface of cancer cells activates platelets by binding to platelet CLEC-2 in the bloodstream. (B) Thromboinflammation induces expression of podoplanin in vascular endothelial cells, where podoplanin is not expressed in physiological status. (C) Podoplanin expression is induced in inflammatory macrophages and cancer-associated fibroblasts by inflammatory cytokines, although direct evidence shows that podoplanin in these cells activates platelets.