Role of ATM/CXCL12 in macrophage M2 polarization induced by castrated tolerant prostate cancer cells
Objective To explore the role of serine-threonine kinase ATM/CXC chemokine ligand 12(CXCL12)in macrophage M2 polarization induced by castrated tolerant prostate cancer cells.Methods Human prostate cancer cell line C4-2 was selected as the object of study.After transfection of pcDNA3.1 to overexpress CXLC12 and/or small interfering RNAC(siRNA)to silence ATM,C4-2 cells were co-cultured with monocyte line THP-1.Western blot was used to detect levels of ATM and CXCL12.Transwell assay was applied to evaluate the invasion and migration abilities of C4-2 cells and their recruitment effect on macrophages.The mRNA levels of phenotypic markers in M2 macrophages were detected by quantitative PCR.Results After knocking out ATM in C4-2 cells and co-culturing with THP-1 cells,the invasion and migration abilities of C4-2 cells were significantly inhibited(P＜0.05).However,after simultaneously transfecting CXLC12 into cells,the inhibitory effect of ATM siRNA disappeared.Further research had shown that with the knockout of ATM,levels of anti-inflammatory markers CC chemokine ligand 22 and p40 subunit of interleukin 12,as well as the inflammatory factor transforming grouth factor β and interleukin 10,were down-regulated(P＜0.05),accompanied by inhibition of macrophage recruitment and M2 polarization.This effect disappeared after transfection with CXCL12.Conclusion Activation of the ATM/CXCL12 signaling pathway can promote the invasion and migration of castration tolerant prostate cancer cells by enabling the M2 phenotype in the tumor microenvironment to evade immune suppression.
万方数据
维普
