Platelets involved tumor cell EMT during circulation: communications and interventions

Abstract

Distant spreading of metastatic tumor cells is still the leading cause of tumor death. Metastatic spreading is a complex process, in which epithelial-mesenchymal transition (EMT) is the primary and key event to promote it. Presently, extensive reviews have given insights on the occurrence of EMT at the primary tumor site that depends on invasive properties of tumor cells and the tumor-associated microenvironment. However, essential roles of circulation environment involved in tumor cell EMT is not well summarized. As a main constituent of the blood, platelet is increasingly found to work as an important activator to induce EMT. Therefore, this review aims to emphasize the novel role of platelet in EMT through signal communications between platelets and circulation tumor cells, and illustrate potent interventions aiming at their communications. It may give a complementary view of EMT in addition to the tissue microenvironment, help for better understand the hematogenous metastasis, and also illustrate theoretical and practical basis for the targeted inhibition.

Roles of platelets in tumor invasion and metastasis: A review

“…IMPs produce chemokines CCL2 and CXCL12, which are responsible for recruiting macrophages, and with the assistance of IL-4 and IFN-γ, tumor killing ability of macrophages is activated, thereby inhibiting the growth of primary tumors. Studies have confirmed that there are IMPs in colon cancer [ 95 , 96 ] ( Figure 4 ②). However, IMPs activate endothelial cells in the circulating blood flow, promote the adhesion of tumor cells to endothelial cells, produce EMT and promote tumor metastasis.…”

L1CAM expression in either metastatic brain lesion or peripheral blood is correlated with peripheral platelet count in patients with brain metastases from lung cancer

“…Reciprocally, previous studies have also indicated that inhibition of TGF-β1 signaling or L1CAM signaling abrogated these effects and likewise inhibited platelet-derived TGF-β1/L1CAM/integrin/NF-kappaB pathways induced tumor invasion metastasis cascade ( 23 , 25 , 33 , 40 ). In addition, since platelets express integrins while vascular endothelial cells also express the L1CAM ( 41 ), and L1CAM–integrin interactions can occur in trans(between different cells) ( 15 ), it is feasible that L1CAM–integrin signaling will contribute to significant platelet adhesion and tumor-associated thrombosis, which is thought to be important for the tumor cell arrest and migration in blood circulation when tumor cells detach from the primary site and intravasate into blood vessels ( 42 , 43 ). Taken together, these studies suggest that the L1CAM plays a crucial role in the bidirectional cross-talk between cancer and platelets.…”

Perspectives of metal-organic framework nanosystem to overcome tumor drug resistance

“…In addition, Huang et al summarized that multiple checkpoint blockades, including PD-1 and cytotoxic T lymphocyte antigen-4 (CTLA-4), developed an immunosuppressive TME in melanoma tumors [65] . Recently, Saha et al revealed that cancer cells can interact with platelets entering TME to produce chemoresistance [80] . The platelet has been increasingly found to work as an important activator to induce epithelial-mesenchymal transition (EMT), while EMT is the primary and key event in promoting the distant spreading of metastatic tumor cells [81] .…”

“…Recently, Saha et al revealed that cancer cells can interact with platelets entering TME to produce chemoresistance [ 80 ] . The platelet has been increasingly found to work as an important activator to induce epithelial-mesenchymal transition (EMT), while EMT is the primary and key event in promoting the distant spreading of metastatic tumor cells [ 81 ] . In another study, indoleamine 2,3-dioxygenase (IDO) in TEM was found to catalyze the metabolism of L-tryptophan to L-kynurenine, thus inhibiting the increase of effector T cells and promoting the growth of regulatory T (Treg) cells [ 70 ] .…”