CYTOKINES MAY INFLUENCE TUMOR-GROWTH AND SPREAD - AN IN-VITRO STUDY IN 2 HUMAN CANCER CELL-LINES

Tumor spread may be favored by a reduced production and/or an enhanced degradation of extracellular matrix components (collagen, fibronectin , laminin). Most tumor cell behavior, from growth to spread, may be re gulated by cytokines, the exact roles of which, however, are not yet f ully understood. We here evaluate the effects of some cytokines (epide rmal growth factor, transforming growth factor-beta 1, interleukin-1 a lpha, and interleukin-1 beta) on both cell growth and the production o f the aminoterminal peptide of type III procollagen, the urokinase pla sminogen activator, and the plasminogen activator inhibitor-1 in neopl astic cell lines originating in the pancreas and colon. Cells were sti mulated daily with the above cytokines and the aminoterminal peptide o f type III procollagen, urokinase plasminogen activator, and plasminog en activator inhibitor-1 were measured in the conditioned media. Epide rmal growth factor stimulated cell growth of both cell lines. Transfor ming growth factor-beta 1 counteracted cell proliferation and stimulat ed type III procollagen and plasminogen activator inhibitor-1 producti on only in the colon cancer cell line. Interleukin-1 alpha slightly st imulated cell growth, but inhibited plasminogen activator inhibitor-1 production in both cell lines; interleukin-1 beta did not affect cell growth, but stimulated plasminogen activator inhibitor-1 production by the colon cancer cell line. Our findings suggest that transforming gr owth factor-beta 1 and interleukin-1 beta may have an antidiffusive ef fect. These results confirm that cytokine-producing cells have a poten tial role in stimulating or counteracting tumor growth and spread and also confirm the pivotal role of host-tumor interactions in determinin g the outcome of a particular neoplasia.