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

Abstract

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-1 beta, TGF-beta 1, TNF-alpha 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 humoral factors. Similar tumor cell-host cell interactions may be important in the production of various proteinases in other tumor types.

Highly Active and Removable Ruthenium Catalysts for Transition‐Metal‐Catalyzed Living Radical Polymerization: Design of Ligands and Cocatalysts

“…Here, we have shown that co‐cultures of PC cells with stromal cells derived from various sources could specifically induce MMP‐9 expression in PC cells at the transcriptional level, resulting in higher levels of pro‐MMP‐9 protein in the culture media. This result is in agreement with previous studies demonstrating up‐regulation of pro‐MMP‐9 expression in co‐cultures of a variety of tumor and stromal cells 29–35. Although pro‐MMP‐9 was expressed by both tumor and stromal cells at very low levels when cultured alone, PC cells were responsible for the increased pro‐MMP‐9 levels in the co‐culture, as shown in the experiments with fixed cells and conditioned media.…”

Differential regulation of metalloproteinase production, proliferation and chemotaxis of human lung fibroblasts by PDGF, Interleukin‐1β and TNF‐α

“…14,15 Cytokines including TGF-a and IL-1b augmented the synthesis of MMP-9 in murine skin fibroblasts. 31 Our experiments suggested that MMP-1 and MMP-2 were spontaneously released, whereas MMP-3 and MMP-9 were not from human lung fibroblasts. In addition, MMP-3 and MMP-9 were also not induced by PDGF alone.…”

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

“…Similarly, we detected only pro-MMP-9, and not active MMP-9, in peripheral blood mononuclear cell culture supernatant from KD patients (Q. Yu and coworkers unpublished data). Cytokines known to increase MMP-9 production include interleukin-1 (IL-1) (6, 17), IL-2 (21), tumor necrosis factor alpha (20), alpha interferon (IFN-␣), IFN-␥ (13), and transforming growth factor beta (38). Of these cytokines, IL-2, tumor necrosis factor alpha, and IFN-␥ are elevated in KD.…”