INVESTIGATION OF POSSIBLE AUTOCRINE FUNCTIONS FOR RAT GRO CINC (CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT)/

Rat cytokine-induced neutrophil chemoattractant (CINC) is an eight kil odalton polypeptide originally purified from media conditioned by inte rleukin-1beta stimulated 52E, an epitheloid clone derived from normal rat kidney (NRK) cells. Using a fibroblastic clone of the NRK cells, 4 9F, we found expression of the CINC gene to be induced by either serum or cytokines in growth-arrested cultures within 1 hour of stimulation . There was no observable CINC expression in exponentially growing cel ls in the absence of cytokine stimulation. CINC protein had no signifi cant effect on H-3-thymidine incorporation or growth rate of NRK49F. W e have observed that CINC is constitutively produced by some transform ed NRK cells, clone RC20, suggesting an association with the expressio n of a transformed phenotype. Unlike the parent 49F, RC20 cells are ca pable of growth in soft agar and serum-free media and form highly meta static tumors in nude mice. We have examined the possible autocrine fu nctions of CINC and its possible links to the expression of the transf ormed phenotype by these cells. The use of a blocking CINC polyclonal antibody demonstrated that CINC did not function as an autocrine growt h factor for RC20. Though CINC is a potent chemoattractant for neutrop hils, it did not induce migration of either RC20 or 49F cells. CINC on ly moderately promoted adhesion of RC20 cells when used as a matrix pr otein. These data do not support the hypothesis that production of CIN C by the RC20 cells provides an obvious advantage for the transformed cells constitutively producing it. (C) 1993 Wiley-Liss, Inc.