RIPK3-mediated M2-type polarization of macrophages in colorectal cancer liver metastasis

Objective: To study the role of M2-type polarization in macrophages mediated by receptor interacting serine/threonine kinase 3 (RIPK3) in colorectal cancer liver metastasis (CRLM) and its related mechanisms.Methods: Colon tumors and their paracancer tissues were collected from CRLM patients for pathological analysis.The expressions of RIPK3, CD68 and Arg-1 were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).The peripheral blood of CRLM and colon cancer patients was collected, and the macrophage typing was detected by flow cytometry.Serum levels of interleukin-1β, IL-6, inducible nitric oxide synthase (iNOS), IL-4, transforming growth factor-β (TGF-β) and IL-10 were detected by ELISA.PLK-RIPK3 and PLK-NC were transfected into THP-1 cells by lentivirus, and M2-type macrophages were induced by PMA/IL4.The polarization degree of the two groups of cells was detected by RT-qPCR and western blotting.The two groups of cells were co-incubated with human colon cancer cell line WiDr, respectively; the migration, invasion changes and expression of metastasis associated in colon cancer 1 (MACC1) and MYC proto-oncogene (c-MYC) of WiDr cells were detected.Results: The pathological structure of colon tumors in CRLM patients was consistent with liver metastasis of intestinal adenocarcinoma.Compared with paracancer tissues, the expression of RIPK3 in CRLM tumor tissues decreased while the expressions of CD68 and Arg-1 increased.Compared with colon cancer patients, the peripheral blood of CRLM patients was more enriched with M2-type macrophages; the serum contents of IL-4, TGF-β and IL-10 increased while the contents of IL-1β and iNOS decreased.Compared with the WiDr+PLK-NC-THP-1 group, the WiDr+PLK-RIPK3-THP-1 group was less induced into M2 macrophages; the ability to promote migration and invasion of WiDr cells and the expressions of MACC1 and c-MYC decreased.Conclusion: The expression of reduced RIPK3 promotes the expressions of MACC1 and c-MYC and tumor metastasis in colorectal cancer cells by inducing M2-type polarization of macrophages.