Platelets are potentially involved in tumor angiogenesis because they contain numerous angiogenic factors (e.g., VEGF, bFGF, PDGF, PAI-1). Clinical studies revealed that platelets are the main source of the serum VEGF concentration typically correlated with poor prognosis in cancer patients.
Although the mechanisms of growth factor release from platelets have not been entirely resolved, in vitro experiments have demonstrated that growth factor release depends on platelet activation and aggregation. Although platelet secretion occurs independently of platelet aggregation, release of growth factors becomes detectable only above threshold doses of thrombin and other platelet agonists at which platelet aggregation is inevitable. A further prerequisite for the promoting effect of platelets on the formation of microvascular tubuli seems to be direct cell-to-cell interactions between platelets and the proliferating endothelium.
Growth factors, especially VEGF, are secreted by a high percentage of malignant animal and human tumors, and also by stromal cells adjacent to the tumors. Only a few exceptional tumors are known that express little or no VEGF mRNA and protein. These tumors, renal papillary carcinoma and lobular breast cancer, are found to be almost avascular and to have better prognosis because of their minor inva-siveness. A positive correlation between platelets and disease progression has only been reported for advanced cancer diseases characterized by dense vascularization, invasive-ness, and metastatic diseases.
VEGF may be taken up by platelets from blood plasma since there is a strong correlation between plasma VEGF levels and serum VEGF load per platelet in tumor patients. Therefore, VEGF content in platelets might be not only a result of increased protein syntheses in megakaryocytes in response to tumor released cytokines and growth factors, but also a consequence of endocytosis of tumor-derived VEGF by circulating platelets .
In conclusion, tumor microvessels do not express a highly prothrombotic environment favoring platelet aggregation. Hence, platelets do not become sufficiently activated to release angiogenic growth factors at sites of tumor angio-genesis. It is more probable that platelets take up and preserve angiogenic growth factors released by tumor cells. The role of platelets as a reservoir for angiogenic growth factors in tumor growth has not yet been identified.
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