질편모충 감염 전립선암세포의 증식 및 침습에 지방세포가 미치는 영향

Abstract

BACKGROUND. Trichomonas vaginalis(Tv) has been detected in urine or prostatic tissue of prostatitis, benign prostatic hyperplasia, and prostate cancer (PCa). Obesity is associated with increased incidence of PCa. Periprostatic adipocyte is known to promote PCa aggresiveness. Here we investigated whether Tv could be involved in progression of PCa, and crosstalk between prostate cancer cell infected with Tv and adipocyte may affect on progression of PCa. METHODS. 3T3-L1 cell (mouse preadipocyte cell line) was differentiated to mature adipocyte using MDI medium. TRAMP-C2 cell (mouse prostate cancer cell line) and T. vaginalis isolate (T016) were grown in DMEM and TYM media, respectively. Trichomonad-conditioned medium (TCM) and adipocyte-conditioned medium (ATCM) was obtained from culture supernatant of TRAMP-C2 cell (mouse PCa cell) infected with Tv (TCM) or adipocyte reacted with TCM, respectively. To detect cytokine and its mRNA expression, we performed ELISA, real-time PCR. Cytokine receptor expression was confirmed by fluorescence microscope. Epithelial-mesenchymal transition (EMT) was examined by western blotting. Proliferation (CCK-8 assay), wound healing and matrigel invasion assay were evaluated for PCa progression. RESULT. When TRAMP-C2 cell was stimulated with Tv, protein and mRNA levels of CXCL1, CCL2 were increased. Adipocyte treated with TCM showed increased production of CXCL1, CCL2, IL-6 and TNF-α. When 3T3-L1 reacted with CM or TCM, preadipocyte was more migrated to TCM than that of CM. The TCM and ATCM including inflammatory and tumorigenic cytokines induced proliferation, migration and invasion of TRAMP­C2 cell, but more increased in ATCM than TCM. TRAMP-C2 cell reacted with ATCM caused epithelial­mesenchymal transition (EMT) by decreasing the epithelial markers (E­cadherin) and increasing mesenchymal markers (Vimentin). Neutralization of each cytokine receptor with anti-cytokine receptor antibody (CXCR2, CCR2 and IL-6 receptor) before ATCM treatment significantly reduced the proliferation, migration and invasion of prostate cancer cell. CONCLUSION. Taken together, Tv induced progression of prostate cancer cell. ATCM showed increased proliferation, migration and invasion of prostate cancer cell through cytokine-cytokine receptor signal pathway (CXCL1, CCL2, IL-6). Our result therefore show that the inflammatory response by prostate cancer cells infected with Tv may induce the promotion of PCa via crosstalk with adipocytes.