Exchange of cellular components between platelets and tumor cells: impact on tumor cells behavior

Abstract

Background: Platelets are active players in tumorigenesis, although the exact interactive mechanisms and their direct impact on tumor cells remain largely unknown. Methods: Bidirectional transference of lipids, proteins and RNA between platelets and tumor cells and its impact on tumor cell behavior and tumor process are analyzed in this work. Phenotypic, genetic and functional modifications induced by platelets were analyzed both in tumor cell lines and in circulating tumor cells (CTCs). Results: Data from these assays showed that platelets transferred structural components to tumor cells with higher efficiency than tumor cells to platelets (p = 0.001). This biological interplay occurred by direct contact, internalization or via extracellular vesicles. As a result, tumor cells acquired platelet markers (CD61 and CD42), showed decreased EpCAM, expressed epithelial-to-mesenchymal transition markers, and increased proliferation rates. Moreover, we were able to detect CD61 in CTCs from early and advanced prostate cancer. Conclusions: Our results demonstrated, for the first time, that platelets educate tumor cells by highly efficient transference of lipids, proteins and RNA through different mechanisms. These results suggest that tumor cells and CTCs might acquire highly dynamic and aggressive phenotypes due to platelets interaction including EMT, stem-like phenotype and high proliferative rates.

Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance

“…An important mechanism for CTC survival is the formation of heterotypic clusters with different cells, such as MDSCs (Sprouse et al, 2019), stromal cells like fibroblasts (Hurtado et al, 2020) and/or neutrophils (Szczerba et al, 2019), macrophages (Hamilton and Rath, 2017), and DCs (Wei et al, 2019b). Furthermore, platelets also play a role in the immune evasion by facilitating the escape of CTCs from MHC class I-mediated recognition by NK and T cells by the transfer of MHC class I onto the tumor cell surface (Placke et al, 2012a;Rodriguez-Martinez et al, 2022). In addition, platelets provide CTCs with a coating shield that helps their survival from the physical stress in the blood and from anoikis (Lucotti and Muschel, 2020).…”

Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside

“…In fact, a recent study suggested that prostate CTCs cocultured with platelets showed decreased EpCAM expression levels but elevated platelet marker CD61, accompanied by a higher proliferation rate during EMT. The results indicated that CD61, rather than EpCAM, might be an alternative diagnostic marker in this situation [ 107 ].…”

Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

“…Tumor-Educated Platelets (TEPs) reprogram the behavior of CTCs via a direct interaction accompanied by exchanging RNA, lipids, and proteins (i.e., beta-3 integrin marker CD61) [ 206 ]. This trafficking event creates a supportive microenvironment for CTCs and facilitating their immune evasion via protecting them from natural killer cells [ 207 ].…”

“…This trafficking event creates a supportive microenvironment for CTCs and facilitating their immune evasion via protecting them from natural killer cells [ 207 ]. The ability of platelets to alter tumor cells’ phenotypes and genetic content promote cell growth and plasticity [ 206 ]. During the course of tumor metastases initiation, TEPs facilitate EMT to lead the tumor towards metastases [ 206 ].…”