Platelets and Metastasis: New Implications of an Old Interplay

Abstract

During the process of hematogenous metastasis, tumor cells interact with platelets and their precursors megakaryocytes, providing a selection driver for the metastatic phenotype. Cancer cells have evolved a plethora of mechanisms to engage platelet activation and aggregation. Platelet coating of tumor cells in the blood stream promotes the successful completion of multiple steps of the metastatic cascade. Along the same lines, clinical evidence suggests that anti-coagulant therapy might be associated with reduced risk of metastatic disease and better prognosis in cancer patients. Here, we review experimental and clinical literature concerning the contribution of platelets and megakaryocytes to cancer metastasis and provide insights into the clinical relevance of anti-coagulant therapy in cancer treatment.

Keywords: anti-coagulant therapy; cancer metastasis; coagulation; megakaryocytes; platelets; thromboembolism.

Figure 1

Mechanisms of tumor cells-platelets interaction. Tumor cells generate platelet activation and the formation of microclots on their surface through several mechanisms, including expression of hemostatic factors and adhesion proteins, either on their surface or on the surface of shedded extracellular vesicles, or though the generation of a pro-thrombotic intravascular metastatic niche involving other stroma cells.

Figure 2

Tumor cell-platelet interplay during the metastatic cascade. Diagram depicting the intravascular steps of the metastatic cascade that are supported by platelet interaction with tumor cells and their timeline. Therapeutic approaches that interfere with the different steps of tumor cells dissemination are indicated in gray.