Platelet Effects on Ovarian Cancer

Abstract

Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer.

Antitumor and Antiangiogenic Effects of Aspirin-PC in Ovarian Cancer

“…Indeed, this would be consistent with the compelling evidence that late stage cancer patients, including those with ovarian cancer have elevated platelet counts (thrombocytosis) that results in a much higher risk for developing deep vein thrombosis than the general population (27, 49). As indicated earlier, we and others have indeed reported that platelets promote cancer cell proliferation, in part by promoting epithelial-mesenchymal transition (EMT), as well as promoting the translocation from the primary tumor into circulation and ultimately from the blood to tissue sites where metastatic growth and angiogenesis occurs, a process facilitated by the local release of platelet derived VEGF, TGFβ and PDGF (7, 25, 27). Thus, aspirin’s unique action to irreversibly inactivate platelets (via acetylation of COX-1) may be a very powerful mechanism to block the progression of cancer, a concept that has been considered by others (3, 5, 50).…”

“…Following initial response to therapy, there is frequently rapid emergence of drug resistance (6, 7). In a recent study, we also demonstrated that platelets play an important role in tumor regrowth following withdrawal of anti-VEGF therapy (8).…”

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data

“…Recently, we reported that pretreatment platelet count predicts EHM of HCC . Indeed, it has been reported that a high platelet count is associated with systemic metastasis of other human cancers . Mechanistically, platelets have been shown to functionally promote the invasion and metastasis of cancer cells through a variety of molecular mechanisms .…”

Mechanisms and Targets Involved in Dissemination of Ovarian Cancer

“…Tumor-associated macrophages have been identified as important contributors to metastasis, based on their shift from an antitumoral (M1) to a pro-tumoral (M2) subtype in ovarian cancer (40,41). It has also been shown that platelets can interact with ovarian cancer cells, resulting in activation of pathways which mediate induction of EMT, extravasation, invasion, and metastasis (42)(43)(44). The contents released from activated platelets into the peritumoral space can induce tumor cell proliferation and extravasation of ovarian cancer cells (42).…”