The role of blood platelets in tumor progression and metastasis

Cancer is among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.8 million cancer-related deaths in 2015 (World Health Organization, 2017). Early studies characterizing alterations affecting oncogenes and tumor suppressors helped to establish the fundamentals of cancer biology. During the last decade, anti-cancer therapies primarily focused on targeting tumor cells. However, cumulated experimental and preclinical data indicate that tumor progression and metastasis are not cell-autonomous processes, but rather involve multiple interactions with the tumor microenvironment, including blood vessels, immune cells, bone-marrow derived cells, platelets, growth factors, cytokines and extracellular matrix components. This milieu stimulates cancer cell growth and invasion, prevents them from being recognized by the immune system and promotes their survival in the circulation until they extravasate and seed at distant organs to form metastases. Currently, it is believed that cellular and molecular components of the tumor microenvironment constitute a barrier which protects against certain anti-cancer drugs and favors development of resistance against therapeutic approaches.

The modulation of the tumor microenvironment therefore represents a promising approach for the development of new therapeutic targets to treat human cancers.

Platelets are small anucleated cellular fragments, derived from megakaryocytes in the bone marrow. Beyond their central role in hemostasis, recent findings indicate that platelets may modulate many hallmarks of cancer. Platelets are proposed to support tumor angiogenesis and growth, protect tumor cells from immune system responses and induce epithelial-mesenchymal transition. Moreover, platelets facilitate the recruitment of circulating tumor cells to the vessel wall and promote their extravasation, thereby supporting tumor metastasis. In addition, meta-analysis of clinical studies has revealed that the intake of aspirin to inhibit platelet function may reduce the incidence and spread of solid tumors. Although these experimental and clinical evidences suggest that platelets are involved in tumor development and metastasis, the underlying molecular mechanisms have not been established.

Our research group focus on the functions of platelets in the control of several steps of cancer development, including tumor growth, angiogenesis and tumor metastasis. To address the role of platelet signaling in these processes, we use in vivo mouse models of several human cancers, such as colon, breast, melanoma, lung and hepatocellular carcinoma. We evaluate the role of platelets by using anti-platelet drugs and inhibitors, blocking antibodies and genetically modified mice. Besides in vivo studies, we employ cutting-edge microscopy techniques and several original in vitro models in order to study the interaction of platelets with tumor, immune or endothelial cells. Our aim is not only the expansion of our knowledge on the role of platelets in fundamental mechanisms of tumor progression and metastasis, but also the identification of novel approaches for the development of anti-cancer therapies.