Stürzl M, Brandstetter H, Zietz C, Eisenburg B, Raivich G, Gearing D P, Brockmeyer N H, Hofschneider P H
Abteilung Virusforschung, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Oncogene. 1995 May 18;10(10):2007-16.
By means of a combined in vitro and in vivo analysis we provide evidence that IL-1 beta and PDGF-B, but not OSM (oncostatin M) or IL-6, are major mitogens for the spindle cells of Kaposi's sarcoma (KS) in vivo. PDGF-B and IL-1 beta stimulated proliferation of cultivated KS spindle cells in vitro. Analysis of gene expression in vivo revealed that both factors as well as the PDGF beta-receptor are present in KS lesions. By contrast, IL-6 had no effect and OSM inhibited proliferation of cultivated KS spindle cells. Again, the effect of these factors on cultivated KS spindle cells in vitro was reflected by the gene expression observed in KS lesions in vivo. Neither the expression of IL-6 receptor nor of OSM could be detected in KS lesions by in situ hybridization. Moreover, in situ hybridization revealed an identical pattern of gene expression in cultivated KS spindle cells and KS spindle cells in vivo with respect to the above-mentioned cytokines [PDGF-B, IL-1 beta, IL-1 alpha, IL-6, OSM] and their receptors [PDGF beta-receptor, gp130, IL-6 receptor, leukemia inhibitory factor (LIF) receptor]. This further supported the suitability of cultivated KS spindle cells as an in vitro model in order to determine which cytokines may activate proliferation of KS spindle cells in vivo.
通过体外和体内联合分析,我们提供证据表明,白细胞介素-1β(IL-1β)和血小板衍生生长因子-B(PDGF-B),而非抑瘤素M(OSM)或白细胞介素-6(IL-6),是体内卡波西肉瘤(KS)梭形细胞的主要促有丝分裂原。PDGF-B和IL-1β在体外刺激培养的KS梭形细胞增殖。体内基因表达分析显示,这两种因子以及PDGFβ受体均存在于KS病变中。相比之下,IL-6无作用,OSM抑制培养的KS梭形细胞增殖。同样,这些因子对体外培养的KS梭形细胞的作用反映在体内KS病变中观察到的基因表达上。通过原位杂交在KS病变中未检测到IL-6受体或OSM的表达。此外,原位杂交显示,在培养的KS梭形细胞和体内KS梭形细胞中,上述细胞因子[PDGF-B、IL-1β、IL-1α、IL-6、OSM]及其受体[PDGFβ受体、gp130、IL-6受体、白血病抑制因子(LIF)受体]的基因表达模式相同。这进一步支持了培养的KS梭形细胞作为体外模型的适用性,以确定哪些细胞因子可能在体内激活KS梭形细胞的增殖。