Human Cancer and Platelet Interaction, a Potential Therapeutic Target

Abstract

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce cancer-related thrombosis. Here, we discuss the potential function of platelets in regulating cancer progression and summarize the factors and signaling pathways that mediate the cancer cell-platelet interaction.

The “Janus Face” of Platelets in Cancer

“…In the latter case, the pathology is called paraneoplastic thrombocytosis [22,23]. According to the clinical evidence that patients with a high platelet count have a higher risk to develop venous thromboembolism (VTE) [24], cancer patients frequently show activated coagulation pathways, resulting in a four-fold increase in thrombosis risk [25].…”

Modulating barriers of tumor microenvironment through nanocarrier systems for improved cancer immunotherapy: a review of current status and future perspective

“…The research found that the removal of platelets caused bleeding at the tumor site and decreased tumor vasculature leakiness. Platelet elimination in thrombocytopenic mice also improved the effectiveness of breast cancer therapies (Wang et al, 2018b). To avoid potential bleeding in normal organs caused by low platelet counts, a recent study by Li et al (2017) designed a tumor microenvironment-responsive NP worthy of distributing antiplatelet antibody R300 to specifically reduce platelets in cancer cells, thereby increasing endothelial dysfunction and enhancing the distribution of nanomedicine to tumors.…”

Podoplanin is indispensable for cell motility and platelet-induced epithelial-to-mesenchymal transition-related gene expression in esophagus squamous carcinoma TE11A cells

“…Besides the PDPN-CLEC-2 axis, several interactions with cell surface molecules have been reported for tumor cell-induced platelet aggregation, including interactions between ADMA10, galectin-3,α V β III and CD97 on tumor cells and α 6 β 1 , gpVI, α IIb β III and an unidentified target on platelets, respectively [18,20,36,37]. In addition to direct contact, tumor-secreted factors such as thrombin, matrix metalloproteinases and ADP have also been suggested to cause platelet aggregation [18,36,38]. Studies are currently underway to elucidate the mechanisms of platelet aggregation by TE11A cells.…”

“…The signaling module 2 is TGF-β receptor signaling pathway and is activated by TGF-β from platelets. All the other signaling pathways activated by platelets are collectively referred to as signaling module 3, which possibly includes platelet-cancer cell direct contact [17,20], platelet-derived lysophosphatidic acid [37], S1P [4], PDGF, and microRNA939 [36]. Upon interaction with PDPN, platelets activate signaling module 1 and/or module 3 in parallel with signaling module 2, thereby resulting in the expression of N-cadherin and Vimentin proteins.…”