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Review
. 2023 Feb 17;15(4):1282.
doi: 10.3390/cancers15041282.

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

Selin Oncul  1 , Min Soon Cho  1
Affiliations
Review

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

Selin Oncul et al. Cancers (Basel). .

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.

Keywords: angiogenesis; immune system; metastasis; ovarian cancer; platelet; thrombosis; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The tumor microenvironment (TME) of ovarian cancer. Tumor cell-induced activated platelets engage with endothelial cells, pericytes, mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), adipocytes, immune cells, and extracellular matrix (ECM) elements through direct interaction or by releasing various modulatory factors and platelet microparticles. Platelets promote the extravasation, differentiation, and activation of these cells, which, in turn, contribute to the hyper-responsiveness of platelets and thrombosis in a positive feedback loop.
Figure 2
Figure 2
The pro-angiogenic role of platelets in cancer. The interaction between platelets, endothelial cells, and pericytes supports the extravasation of immune cells, mesenchymal stem cells (MSCs), endothelial precursor cells (EPCs), and tumor cells. Platelets also release proangiogenic factors that promote new blood vessel formation and facilitate tumor growth. The newly formed cancer-associated blood vessels are branched, leaky, and less supported by pericytes. Insufficient oxygen and nutrient supplies lead to hypoxic and necrotic areas in the tumor. Platelet-targeting strategies can restrict neoangiogenesis.
Figure 3
Figure 3
The molecules that mediate the interaction between platelets and immune cells in the tumor immune microenvironment (TIME). Activated platelets and immune cells in the TME communicate through various receptors and ligands or secreted modulatory factors, and these interactions can be targeted for the therapy of ovarian cancer.
See this image and copyright information in PMC

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