Study of molecular mechanism of tumor microenvironment promoting metastatic castration resistant prostate cancer progression
Objective To explore the molecular mechanism of prostate cancer's acquired castration resistant metastasis ability.Methods MiR-130a levels in exosomes derived from peripheral blood samples of healthy volunteers(Control group),local prostate cancer(Local PC group)patients and metastatic castration resistant prostate cancer(mCRPC group)patients were collected,isolated and determined.The cancer tissue of the above prostate patients was collected.The proportion of M2-like macrophages infiltrating in the cancer tissues were measured by flow cytometry.Monocyte chemotactic protein-induced protein 3(MCPIP3)expression levels in cancer tissues were determined by western blot.The levels of tumor necrosis factor-α(TNF-α)and interleukin-17A(IL-17A)in cancer tissues were measured by enzyme-linked immunosorbent assay(ELISA).In vitro co-cultured system of mouse RAW264.7 macrophages and human prostate cancer LNCaP cells was established.Lipopolysaccharide(LPS)and IL-4 were used to induce RAW264.7 cells Ml and M2 polarization,respectively.The proliferative ability of LNCaP cells in co-cultured system was determined in the presence or absence of enheterulamine.Results Compared with Control group,the relative expression level of miR-130a in exosomes of patients in mCRPC group were significantly increased(P＜0.05),but there was no significant difference in patients of Local PC group(P＞0.05).Compared with the patients in Local PC group,the relative level of miR-130a in plasma derived exosomes of mCRPC group was significantly increased,the percentage of M2-like macrophages infiltrating in the cancer tissues,the relative expression level of MCPIP3 and the level of IL-17A were up-regulated in cancer tissues(P＜0.05),while there was no significant difference in the level of TNF-α(P＞0.05).The proliferative and castration resistant proliferative ability of LNCaP cells in co-cultured system with M2-like macrophages were higher than that of LNCaP cells in co-cultured system with M1-like macrophages.Conclusions Prostate cancer cells released high levels of miR-130a through exosomes to change the tumor microenvironment,and to induce macrophages M2-like polarization and extensively infiltrated cancer tissues,with releasing high level of IL-17A,so as to form a tumor immune microenvironment that promotes prostate cancer obtaining castration resistant growth and metastasis.
Prostate cancerCastration resistant metastasisTumor microenvironmentMicroRNA-130aMonocyte chemotactic protein-induced protein 3Interleukin-17A
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