Activation of the signaling transduction pathways mediated by oncostatin M (OSM) requires the binding of the cytokine to either type I OSM receptor (leukemia inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the present work we have developed an enzyme-linked immunosorbent assay detecting a soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma tumor cell lines. sOSMR was also present in sera of healthy individuals, with increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA was carried out, and it encoded for a 70-kDa protein consisting of a half cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin-like domain, and the first half of a second cytokine binding domain with cysteines in fixed positions. Analysis of the soluble receptor distribution revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR was able to bind OSM and interleukin-31 when associated to soluble gp130 or soluble interleukin-31R, respectively, and to neutralize both cytokine properties. We have also shown that OSM could positively regulate the synthesis of its own soluble receptor in tumor cells.
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机译：抑癌素 M （OSM） 介导的信号转导通路的激活需要细胞因子与 I 型 OSM 受体（白血病抑制因子受体/gp130）或 II 型 OSM 受体 （OSMR/gp130） 结合。在本工作中，我们开发了一种酶联免疫吸附测定法，用于检测胶质母细胞瘤、肝瘤和黑色素瘤肿瘤细胞系分泌的可溶性 OSMR （sOSMR）。sOSMR也存在于健康个体的血清中，在多发性骨髓瘤中水平升高。对相应的cDNA进行分子克隆，并编码一个70-kDa的蛋白质，该蛋白由一个包含典型WSXWS基序的半细胞因子结合域、一个免疫球蛋白样结构域和第二个细胞因子结合结构域的前半部分组成，半胱氨酸位于固定位置。对可溶性受体分布的分析显示，在肺、肝、胰腺和胎盘中优先表达。当分别与可溶性 gp130 或可溶性白细胞介素-31R 结合时，sOSMR 能够结合 OSM 和白细胞介素-31，并中和这两种细胞因子特性。我们还表明，OSM可以正向调节肿瘤细胞中自身可溶性受体的合成。
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