Expression of the matrix metalloproteinase promatrilysin in coculture of prostate carcinoma cell lines

BACKGROUND. Matrix metalloproteinases (MMPs) are involved in tumor progression. Matrilysin (MMP-7) has been shown to be upregulated in prostatic carcinomas and can increase the invasive capacity of DU-145 cells. Because of the heterogenous nature of prostatic tumors, we examined promatrilysin expression in cocultures containing two different prostatic carcinoma cell lines, DU-145 and LNCaP. METHODS. Using enzyme linked immunosorbent assay (ELISA) analyses, promatrilysin expression was measured in DU-145/LNCaP cocultures and conditioned media cross-cultures. The effects of blocking IL-6 on promatrilysin expression were examined by pretreating conditioned media with IL-6 neutralizing antibody. RESULTS. A significant induction of promatrilysin expression was observed in DU-145/ LNCaP cocultures compared to LNCaP cells alone. In addition, DU-145 conditioned medium induced the same fold induction of promatrilysin as was observed in the cocultures. LNCaP cell conditioned medium did not induce promatrilysin expression in DU-145 cells. Neutralization of IL-6 with neutralizing antibody abrogated DU-145 conditioned media induced promatrilysin expression to baseline levels. CONCLUSIONS. IL-6 secreted by DU-145 cells can induce promatrilysin expression in LNCaP cells. IL-6, in vivo, may act as a paracrine signaling factor that regulates matrix metalloproteinase expression. Therefore, IL-6 may play a role in invasive metastatic processes of a prostate carcinoma.