FIBROBLASTS REGULATE THE MIGRATION OF MCF7 MAMMARY-CARCINOMA CELLS INHYDRATED COLLAGEN GEL

We have defined a tissue culture method suitable to study cell-cell in teractions in an environmental set close to in vivo conditions. It con sists of heterotypic cell populations mixed together inside a collagen gel in a chamber slide for a period of up to 14 days. When the three- dimensional system is saturated, cells will start to move on the plast ic surface as monolayers surrounding the gel, with a characteristic sp eed depending on cell type. Usually fibroblasts move fast, while epith elial cells demonstrate a much lower pace of migration. At any given t ime gel contraction can be measured and thus the rate of cell expansio n, by knowing the distance from the edge of the gel to the leading edg e of cell migration. By using this approach it was found that MCF7 mam mary carcinoma cells display a great variety of morphologies following their mixture with different fibroblastic cell lines. In particular w hen MCF7 cells were mixed with fibroblasts from human fetus, dog thymu s and rat kidney, they migrated up to the leading edge of the fibrobla stic front as isolated single cells or as cellular aggregates, many of which became necrotic in time, or took on an elongated morphology. Se lective necrosis of MCF7 cells was also induced with serum concentrati on of 15% and 20% FCS, but only when they were mixed with fibroblasts. No necrosis was induced in MCF7 cells cultured alone. From these obse rvations it is suggested that necrosis may sometimes favor the detachm ent and infiltration of resistant epithelial tumor cells by increasing their autonomous behaviour. Fibroblasts seem to be instrumental in re gulating this process.