Interactions between Platelets and Tumor Microenvironment Components in Ovarian Cancer and Their Implications for Treatment and Clinical Outcomes

SIMPLE SUMMARY: Despite initially responding to treatment, many ovarian cancers recur because of tumor cell heterogeneity, chemoresistance, and the cancer-promoting and immunosuppressive tumor microenvironment. Recurrent tumors account for the reduced overall and progression-free survival of patients with ovarian cancer. Ovarian cancer is commonly accompanied by thrombocytosis and thrombotic events, which implies that platelets may participate in cancer progression via their association with cancer cells and the tumor microenvironment. This review focuses on platelets’ interactions with cellular and acellular components of the tumor microenvironment, including endothelial cells, mesenchymal stem cells, adipocytes, pericytes, immune cells, and extracellular matrix elements, and discusses how these interactions support the proliferation and metastasis of ovarian cancer cells. It also provides an overview of potential therapeutic strategies that obstruct platelets’ protumor effects by reprogramming the tumor microenvironment. ABSTRACT: Platelets, the primary operatives of hemostasis that contribute to blood coagulation and wound healing after blood vessel injury, are also involved in pathological conditions, including cancer. Malignancy-associated thrombosis is common in ovarian cancer patients and is associated with poor clinical outcomes. Platelets extravasate into the tumor microenvironment in ovarian cancer and interact with cancer cells and non-cancerous elements. Ovarian cancer cells also activate platelets. The communication between activated platelets, cancer cells, and the tumor microenvironment is via various platelet membrane proteins or mediators released through degranulation or the secretion of microvesicles from platelets. These interactions trigger signaling cascades in tumors that promote ovarian cancer progression, metastasis, and neoangiogenesis. This review discusses how interactions between platelets, cancer cells, cancer stem cells, stromal cells, and the extracellular matrix in the tumor microenvironment influence ovarian cancer progression. It also presents novel potential therapeutic approaches toward this gynecological cancer.