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.
Stratton
M S
MS
Department of Radiation Oncology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Sirvent
H
H
Udayakumar
T S
TS
Nagle
R B
RB
Bowden
G T
GT
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D020783:Matrix Metalloproteinase 7