Smooth muscle-derived factor stimulates mobility of human tumor cells

Invasion of normal tissues is a complex process which requires active locomotion of malignant cells. Recent studies have identified a group of proteins which appear to be specific regulators of cell movement. Various strains and lines of fibroblast-like and vascular smooth muscle cells release into culture medium a unique protein activity which causes contiguous sheets of normal epithelial cells (e.g., Madin-Darby canine kidney, MDCK, cells) to spread and separate into individual cells (i.e., to scatter). Crude conditioned medium and partially purified MDCK scattering activity derived from human iliac artery smooth muscle cells (HIAS) scattered several lines of human squamous carcinoma cells (FaDu and A253) and markedly stimulated migration of carcinoma cells out of multicellular spheroids onto plastic culture surfaces. The scattering activities for MDCK and carcinoma cells showed similar sensitivities to temperature, trypsin treatment, and alteration of pH; both activities were blocked in the presence of cycloheximide. Unlike HIAS-derived factor, a similar MDCK scattering factor derived from ras-transformed NIH 3T3 cells did not scatter human carcinoma cells. These findings indicate that specific normal tissue-derived proteins may affect the mobility of tumor cells. Further studies of such proteins may yield insights into the mechanisms of tumor cell locomotion and tumor invasion.