The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Abstract

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet⁻cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

Keywords: angiogenesis; cancer biomarker; drug resistance; metastasis; platelet; platelet-derived growth factor.

Figure 1

Platelets and tumor angiogenesis. Interactions between tumor cells and activated platelets result in angiogenic regulators and microRNAs which are delivered by platelets microparticles (MPs) to various cell types of the tumor-microenvironment in favor of neovascularization (see text for details).

Figure 2

Platelets and tumor metastasis. Interactions between tumor cells and activated platelets, on the one hand, upregulate epithelial mesenchymal transition (EMT) facilitators and promote extravasation, and, on the other hand, protect the cancer cells from various dangers during the process of tumor detachment and circulation. As a result, tumor metastasis is promoted with supports of platelet ally (see text for details).