Fig. 2

Contribution of CLEC-2 to platelet tumor cell cross-talk. Tumor cells expressing podoplanin interact with CLEC-2 localized on platelets. Upon podoplanin ligation, hemITAM motif and Syk are phosphorylated by Src. Activated Syk in turn phosphorylates hemITAM, Src and a signaling complex consisting of LAT, SLP-76 and PLCγ2. Finally, PI3K activation leads to platelet activation and secretion of growth factors, e.g., EGF, PDGF, and TGF-β. PDGF induces Akt phosphorylation ensued by osteosarcoma cell proliferation. TGF-β conducts a shift from an epithelial to a mesenchymal phenotype accompanied by increased tumor invasiveness and proliferation