MODULATION OF THE EXPRESSION OF INTERSTITIAL AND TYPE-IV COLLAGENASESIN COCULTURE OF HT1080 FIBROSARCOMA CELLS AND FIBROBLASTS

Members of the metalloproteinase family (MMPs) are known to play a cru cial role in the metastatic cascade. Here, we report some investigatio ns about the synthesis of interstitial and type-IV collagenases (gelat inases A and B) in a model of coculture of human fibroblasts and HT108 0 fibrosarcoma cells. The interstitial collagenase activity, mainly fo und in the conditioned medium of fibroblasts, and its mRNA level were increased in the in vitro coculture model. In contrast, gelatinase A w as produced by both cell types. The HT1080 cells additionally synthesi sed gelatinase B. In coculture, an enhancement of gelatinase A and the presence of its activated form were observed. Northern blot analysis demonstrated that this enzymatic enhancement occurred at a pretranslat ional level. The stimulation of the interstitial collagenase activity was partially mediated through soluble factor(s), whereas increased ge latinase A appeared to require direct cell-cell interactions. The extr acellular matrix component, type-I collagen, stimulated the enzymatic activities released by the individual cells, but it did not modulate t he synthesis of interstitial collagenase in coculture. Our results dem onstrate that distinct MMPs are modulated by distinct mechanisms, all depending on specific interactions between tumour cells and host fibro blasts.