DIFFERENT MECHANISMS OF EXTRACELLULAR-MATRIX REMODELING BY FIBROBLASTS IN RESPONSE TO HUMAN MAMMARY NEOPLASTIC-CELLS

Human breast tumors are often associated with a fibrotic reaction term ed desmoplasia. Tumor cells may indirectly modulate the composition of the extracellular matrix by influencing fibroblast properties. They m ay also directly interact with collagen fibrils leading to retraction of the matrix. We have studied in vitro the influence of various human mammary tumor cells on the proliferation rate of normal human fibrobl asts and on their level of collagen synthesis, as well as their releas e of collagenase activity. Interactions between neoplastic cells and c ollagen matrix were investigated by incorporation of tumor cells in co llagen gels (lattices) and measurement of their retraction. All cells tested (HBL100, SW613, SA52, MDA-MB-231, MCF7, MCF7/6, MCF7 ras, BT20 and T47D) were able to modulate the composition of the extracellular m atrix by one or several of the mechanisms investigated. Our results al so demonstrate an opposite regulation of collagen and collagenase prod uction. The effects on the collagen metabolism and on fibroblast proli feration are probably mediated by soluble cytokines since they are rep roduced by incubating the fibroblasts in the presence of medium condit ioned by tumor cells. The desmoplastic reaction may thus result from d ifferent mechanisms dependent upon tumor cell types.