Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.
Laboratory of Systems Pharmacology and Translational Therapies, Center for Advanced Studies and Technology (CAST), School of Medicine, "G. d'Annunzio" University, 66100 Chieti, Italy.
Cells. 2022 Feb 18;11(4):725. doi: 10.3390/cells11040725.
Metastasis requires that cancer cells survive in the circulation, colonize distant organs, and grow. Despite platelets being central contributors to hemostasis, leukocyte trafficking during inflammation, and vessel stability maintenance, there is significant evidence to support their essential role in supporting metastasis through different mechanisms. In addition to their direct interaction with cancer cells, thus forming heteroaggregates such as leukocytes, platelets release molecules that are necessary to promote a disseminating phenotype in cancer cells via the induction of an epithelial-mesenchymal-like transition. Therefore, agents that affect platelet activation can potentially restrain these prometastatic mechanisms. Although the primary adhesion of platelets to cancer cells is mainly independent of G protein-mediated signaling, soluble mediators released from platelets, such as ADP, thromboxane (TX) A, and prostaglandin (PG) E, act through G protein-coupled receptors (GPCRs) to cause the activation of more additional platelets and drive metastatic signaling pathways in cancer cells. In this review, we examine the contribution of the GPCRs of platelets and cancer cells in the development of cancer metastasis. Finally, the possible use of agents affecting GPCR signaling pathways as antimetastatic agents is discussed.
转移需要癌细胞在循环中存活、在远处器官定植和生长。尽管血小板是止血、白细胞在炎症中的迁移以及血管稳定性维持的核心贡献者，但有大量证据支持它们通过不同机制在支持转移中发挥重要作用。除了与癌细胞的直接相互作用，从而形成白细胞等异聚体外，血小板还释放分子，通过诱导上皮-间充质样转化，促进癌细胞的扩散表型。因此，影响血小板激活的药物可能会抑制这些促转移机制。虽然血小板与癌细胞的主要初始黏附主要独立于 G 蛋白介导的信号转导，但从血小板释放的可溶性介质，如 ADP、血栓烷（TX）A 和前列腺素（PG）E，通过 G 蛋白偶联受体（GPCR）作用，引起更多血小板的激活，并驱动癌细胞中的转移信号通路。在这篇综述中，我们研究了血小板和癌细胞的 GPCR 在癌症转移发展中的作用。最后，讨论了影响 GPCR 信号通路的药物作为抗转移药物的可能用途。
