Marked induction of gelatinases, especially type B, in host fibroblasts by human ovarian cancer cells in athymic mice

✍ Scribed by Etsuko Miyagi; Hidetaro Yasumitsu; Fumiki Hirahara; Yoji Nagashima; Hiroshi Minaguchi; Kaoru Miyazaki; Makoto Umeda

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 807 KB
• Volume: 13
• Category: Article
• ISSN: 0262-0898
• DOI: 10.1007/bf00133613

✦ Synopsis

Two human ovarian adenocarcinoma cell lines, MCAS-3 and OVISE-3 were found to secrete little of any type of gelatinase in tissue culture. However, when these cell lines were implanted subcutaneously into nude mice the cyst fluids from the resultant tumors contained gelatinase A and/or B. The enzyme activities, especially of gelatinase B, were much higher in the malignant MCAS-3 tumors than in those of the less malignant OVISE-3 tumor cells. To elucidate the origin of gelatinase B in cyst fluids of the MCAS-3 tumors, murine skin fibroblasts (MSF) were isolated from a subcutaneous tumor in a nude mouse and tested for their proteinase secretion in culture. MSF cells, which secreted some gelatinase A and gelatinase B, were induced to secrete high levels of both enzymes, especially gelatinase B, by co-cultivation with MCAS-3 cells. In addition, gelatinase A activity was induced by incubation of MSF cells with the conditioned medium of either MCAS-3 or OVISE-3 cells, whereas gelatinase B was induced only with that of MCAS-3. Although cytokines or growth factors such as IL-I~, TGE-Ill, TNF-~ or EGF stimulated the secretion of gelatinases A and B from MSF cells, their effects on gelatinase B activity were far less than that of the MCAS-3 conditioned medium. These results indicate that the major part of gelatinase B activity in the cyst fluids of the ovarian tumors is secreted by host interstitial cells stimulated by tumor-derived humorai factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types.