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.

Minimal Residual Disease, Metastasis and Immunity

“…Adhesion of CTCs to endothelial cells (ECs) is a first key step of the extravasation process. The initial attachment of tumor cells to the vessel endothelium depends on the expression of selectin family receptors by ECs such as E-selectin and P-selectin, which interact with their respective ligands expressed by cancer cells [46]. Selectin ligands include the tetrasaccharide sialyl-Lewis X antigen and its isomer sialyl-Lewis A [47].…”

The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors

“…The crucial role of tumor cell-mediated platelet activation for promoting different steps of the metastatic cascade, particularly for those taking place within the bloodstream, has extensively been demonstrated and reviewed during the past decade, e.g., (5)(6)(7)(8)(9)(10)(11)(12)(13). Nevertheless, anti-coagulant therapy is still not routinely implemented in the treatment of cancer patients (13). Therefore, it is the time to ask which aspects of platelet-tumor interaction have been underestimated so far and whether the common preclinical models for studying the effects of platelets on metastasis formation are really clinically meaningful.…”

“…The crucial role of tumor cell-mediated platelet activation for promoting different steps of the metastatic cascade, particularly for those taking place within the bloodstream, has extensively been demonstrated and reviewed during the past decade, e.g., ( 5 – 13 ). Nevertheless, anti-coagulant therapy is still not routinely implemented in the treatment of cancer patients ( 13 ).…”

In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel

“…An increased platelet count is correlated with poor disease-free survival (DFS) and overall survival in various cancers [ 1 , 2 , 3 ], including ovarian cancer (OvCa) [ 4 , 5 , 6 , 7 ]. Indeed, platelets and molecules secreted by platelets affect tumor growth, metastasis and anticancer drug activity [ 8 , 9 , 10 , 11 , 12 ]. In turn, tumor cells can stimulate platelet production and activation, leading to an abnormally increased number of platelets in the blood (thrombocytosis) and to the release of growth factors, cytokines, chemokines and vesicular signals, collectively termed “platelet releasate” (PR) [ 12 , 13 , 14 ].…”