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Platelet microparticles and cancer: An intimate cross-talk

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Abstract

Blood cell-derived microparticles (MP), in general, and platelet MPs (PMPs), in particular, have emerged as important contributors, as well as markers, of the delicate balance between health and disease. They may, on one hand, have beneficial effects by supporting tissue repair and regeneration, as well as hemostasis, but may, on the other hand, be a pro-coagulant promoter leading to the thrombotic events seen in the context of cancer. PMPs can act as a direct tumor growth enhancer through the release of potent growth factors in the tumor micro-environment. Tumor engraftment can also be stimulated by the pro-angiogenic potentials of platelet growth factors released by PMPs. PMPs, by their pro-inflammatory and immunomodulatory functions, can also exert an indirect role in the metastatic multistep process by helping malignant cells to escape from immunological surveillance. The possible detrimental effect of transfusions in cancer patients has been debated for several years and the role played by PMPs present in blood products is receiving specific attention, considering their propensity to trigger thrombosis and support tumors. The intimate PMP–tumors crosstalk may therefore result in pro-thrombotic states and a physiological state favorable to tumor growth, tethering and dissemination. Laboratory and experimental studies are needed to better unveil the contribution of PMPs as coagulation promoters, as well as potential markers and targets to treat cancer.

Introduction

The complex relationship between cancer and thrombosis has long been established since the late 19th century by Armand Trousseau, who highlighted that thrombophlebitis is a premonitory sign of occult malignancy [1]. Venous thromboembolism (VTE) occurs in 15–20% of patients with cancer [2]. In some cancers, thromboembolic diseases are the second most common cause of death, accounting for 44% of deaths after the progression of the cancer itself [3], [4].

Multiple studies focused on the role played by coagulation, tissue factor and platelets and their generated microparticles (PMPs) in the context of cancer, inducing thrombosis [5], [6], [7]. Reciprocally, platelets and their MPs seem to interact with tumors favoring their progression and dissemination. A complex bidirectional relationship therefore exists between the platelets (and the microparticles, MPs) on one hand and tumors on the other [8].

Section snippets

Platelet microparticle generation by tumors

PMPs shed from platelets after physiological activation by agonists like thrombin or collagen [9], [10]. The shed microparticles are endowed with procoagulant properties as they may harbor phosphatidylserine and tissue factor, the major initiator of blood coagulation reactions [11]. Platelet activation, and hence PMP generation, has been described in the context of occult and overt malignancy in the presence or absence of distant spread. Tumor cell-induced platelet aggregation (TCIPA) is a

Effect of PMPs on cancer growth, tethering and spread

If cancer cells are capable of inducing PMP generation through the activation of platelets via multiple mechanisms, reciprocally, PMPs are capable of interacting significantly with tumors through a multitude of direct and indirect mechanisms resulting in their proliferation, tethering and dissemination. They may represent potential targets for anticancer therapy.

It is known that following various functional mechanisms, activated platelets and the ensuing microparticles expose receptors and

Transfusion of blood components and PMPs

Many cancer patients are transfused with red blood cells, platelets or plasma in the context of their initial surgical interventions or as a supportive therapy in conjunction to chemo and radiotherapy. Transfusion may confer a poor prognosis in certain cancers [54], [55]. The presence of MPs and particularly PMPs within the transfused components [56] may affect directly and indirectly tumor growth and dissemination and increase thrombotic risks, in addition to exerting inflammatory and

Conclusions

In physiological conditions, PMPs mediate an important role in balancing health and disease, enhancing tissue repair and regeneration on one hand and hemostasis on the other [59]. In the context of cancer, however, the role of PMPs is only negative. Generated in response to tumor–platelet activation, PMPs act as coagulation promoters implicated in cancer-induced thrombosis and firing back on tumors, enhancing direct tumor growth through their load of growth factors. Furthermore, they help tumor

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