Borycki A G, Smadja F, Stanley R, Leibovitch S A
Laboratoire de Cancérologie Expérimentale, UA 1158, URA 126 CNRS, Institut Gustave Roussy, Villejuif, France.
Exp Cell Res. 1995 May;218(1):213-22. doi: 10.1006/excr.1995.1149.
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 the 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 receptor-CSF-1 complexes. It was not possible to block the L6 alpha 1 proliferation by incubation with anti-CSF-1 antiserum or suramin. However, in L6 alpha 1 myoblasts that were stably transfected with an inducible anti-fms antisense construct, both c-fms protein expression and cell proliferation were more rapidly inhibited under induction and differentiation conditions than parental cells. Furthermore, under these conditions, the c-fms antisense transfected cells also entered myogenic differentiation more rapidly. These results suggest that autocrine regulation by CSF-1 that is intracellular may play a role in the proliferation of muscle cells and that its down-regulation leads to, and may be an obligatory step in, myogenesis.
集落刺激因子-1(CSF-1)和CSF-1受体(c-fms原癌基因产物)在L6α1大鼠成肌细胞系增殖过程中表达,且在分化为肌管的过程中二者表达均下调。生物活性CSF-1被证明由L6α1成肌细胞分泌到培养基中,虽然它们不能结合CSF-1,但获得了细胞表面受体-CSF-1复合物的证据。用抗CSF-1抗血清或苏拉明孵育无法阻断L6α1的增殖。然而,在稳定转染了诱导型抗fms反义构建体的L6α1成肌细胞中,在诱导和分化条件下,c-fms蛋白表达和细胞增殖比亲本细胞受到更快速的抑制。此外,在这些条件下,转染了c-fms反义的细胞也更快地进入成肌分化。这些结果表明,CSF-1的细胞内自分泌调节可能在肌肉细胞增殖中起作用,其下调导致并可能是肌生成中的一个必要步骤。