COLONY-STIMULATING FACTOR-1 (CSF-1) IS INVOLVED IN AN AUTOCRINE GROWTH-CONTROL OF RAT MYOGENIC CELLS

Colony stimulating factor-1 (CSF-1) and the CSF-1 receptor (the c-fms proto-oncogene product) are expressed during the proliferation of the L6 alpha 1 rat myogenic cell line and both are down-regulated during t he differentiation to myotubes, Biologically active CSF-1 was shown to be secreted into the culture medium by L6 alpha 1 myoblasts and while they could not bind CSF-1, evidence was obtained for cell surface rec eptor-CSF-1 complexes, It was not possible to block the L6 alpha 1 pro liferation by incubation with anti-CSF-1 antiserum or suramin, However , in LG alpha 1 myoblasts that were stably transfected with an inducib le anti-fms antisense construct, both c-fms protein expression and cel l proliferation were more rapidly inhibited under induction and differ entiation conditions than parental cells, Furthermore, under these con ditions, the c-fms antisense transfected cells also entered myogenic d ifferentiation more rapidly. These results suggest that autocrine regu lation by CSF-1 that is intracellular may play a role in the prolifera tion of muscle cells and that its downregulation leads to, and may be an obligatory step in, myogenesis. (C) 1995 Academic Press, Inc.