Platelet–cancer interactions: mechanisms and pharmacology of tumour cell‐induced platelet aggregation

Abstract

During haematogenous metastasis, cancer cells migrate to the vasculature and interact with platelets resulting in tumour cell-induced platelet aggregation (TCIPA). We review: 1 The biological and clinical significance of TCIPA; 2 Molecular mechanisms involved in platelet aggregation by cancer cells; 3 Strategies for pharmacological regulation of these interactions. We conclude that pharmacological regulation of platelet-cancer cell interactions may reduce the impact of TCIPA on cancer biology.

The role of platelet activation in tumor metastasis

“…Based on the understanding of platelet-tumor cell aggregate formation, potential inhibitors of cancer progression are being explored [reviewed in [10,12]. Platelets adhesion molecules are involved in mediation of platelet-tumor cell interactions.…”

“…Various human and animal tumor cells were found to be capable of inducing platelet aggregation and activation [e.g. 3,[8][9][10][11]. Any interference in platelet-tumor cell interactions with anti-platelet agents has consistently demonstrated potent anti-metastatic effects [reviewed in 10,12].…”

“…3,[8][9][10][11]. Any interference in platelet-tumor cell interactions with anti-platelet agents has consistently demonstrated potent anti-metastatic effects [reviewed in 10,12]. In this article, the mechanisms of platelet contribution to metastasis are reviewed and possible perspectives for therapeutic application are discussed.…”

Activated Platelets Provide a Functional Microenvironment for the Antiangiogenic Fragment of Histidine-Rich Glycoprotein

“…At sites of blood vessel injury, platelets are activated and aggregate at the site of the damaged endothelium to prevent hemorrhage. Besides their role in hemostasis, platelets contribute to nonhemostatic processes such as immunity, tumor metastasis, and angiogenesis (9)(10)(11). Despite their content of both positive and negative regulators of blood vessel formation, platelets have in several different experimental settings been shown to stimulate angiogenesis (11)(12)(13)(14)(15).…”

Characterization of aberrant pathways across human cancers

“…However, we identified processes that we think are actually more related to cancer than normal cell physiology. For example, platelet activation is enriched in 87% of kidney carcinomas, but only in 6% of uterine adenocarcinomas, which may translate to differences in tumour haemostatic activity or formation of cancer metastases through emergence of platelet-tumour cell aggregates [23] (Figure 1d). Another potentially interesting observation is the major difference in enrichment of the drug metabolism by Cytochrome p450 pathway which is closely related to multiple drug resistance, and also represents a potential therapeutic target [24].…”