Targeting platelet-tumor cell interactions: a novel approach to cancer therapy

Abstract

Metastasis-the dissemination of cancer cells to distant organs-is the leading cause of cancer-related death. Beyond hemostasis, platelets contribute to tumor growth, angiogenesis, and metastasis by secreting factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β). These mediators stimulate tumor cell proliferation, migration, and invasion, fostering a microenvironment that promotes cancer progression. These factors stimulate the proliferation, migration, and invasion of tumor cells, contributing to the formation of a supportive tumor microenvironment that promotes cancer progression. On the other hand, tumor cells interact with platelets through various mechanisms, including the release of procoagulant factors, the expression of adhesion molecules, and induction of platelet activation and aggregation. This interaction forms a protective shield around circulating tumor cells, facilitating their escape from immune surveillance and promoting their infiltration into more distant sites. Platelets also play a significant role in modulating the tumor microenvironment. They contribute to immune suppression by inhibiting T-cell function, promoting the activity of immunosuppressive cells (e.g., myeloid-derived suppressor cells), and protecting tumor cells from immune attack. Understanding the complex interactions between platelets, tumor cells, and targeting platelet-tumor interactions (e.g., inhibiting platelet activation or PDGF signaling) may provide promising strategies. This review synthesizes recent advancements in understanding platelet-tumor crosstalk, with a focus on novel mechanisms such as platelet-derived microparticle-mediated metastasis, immune checkpoint mimicry by tumor-educated platelets, and the paradoxical roles of thrombospondin-1 (TSP-1) in angiogenesis. We critically evaluate emerging therapeutic strategies targeting platelet-tumor signaling and identify unresolved questions, including the role of platelet miRNAs in pre-metastatic niche formation and the efficacy of combinatorial antiplatelet-immunotherapy approaches.

Keywords: Platelet activation; Platelet-derived growth factors; Platelet–tumor cell interaction; Tumor microenvironment; Neoplasm metastasis.