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Melanoma cells secrete follistatin, an antagonist of activin-mediated growth inhibition

机译:黑色素瘤细胞分泌卵泡抑素,它是激活素介导的生长抑制的拮抗剂

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Using a proteomic approach to screen for new growth factors released by melanoma cells, we identified follistatin as a major heparin-binding factor in medium conditioned by the Bowes melanoma cell line. Since follistatin is primarily studied in relation to its neutralization of activin, a member of the transforming growth factor- family of ligands, the expression and function of this receptor system was investigated in a panel of melanoma cell lines and melanocytes. All cell lines expressed activin receptors and showed phosphorylation of Smad signal transduction molecules upon treatment with activin. Secretion of follistatin, either native or after retroviral transduction, efficiently prevented Smad activation or activation of an activin-responsive luciferase reporter construct. In melanocytes, activin treatment led to growth inhibition and induction of apoptosis. These effects were counteracted by cotreatment with follistatin. In summary, we characterized the activin–activin receptor system in melanocytes and melanoma cell lines and found that secretion of follistatin by melanoma cells may represent an effective way to circumvent activin's negative regulatory effects.
机译:使用蛋白质组学方法筛选由黑色素瘤细胞释放的新生长因子,我们确定卵泡抑素是在Bowes黑色素瘤细胞系条件下的培养基中的主要肝素结合因子。由于卵泡抑素主要是针对其与激活素的中和有关的,而激活素是配体的转化生长因子家族的成员,因此在一系列黑素瘤细胞系和黑素细胞中研究了该受体系统的表达和功能。所有细胞系均表达激活素受体,并在用激活素处理后显示Smad信号转导分子的磷酸化。天然或逆转录病毒转导后,卵泡抑素的分泌可有效阻止Smad激活或激活素响应性荧光素酶报道基因构建物的激活。在黑素细胞中,激活素处理导致生长抑制和凋亡诱导。与卵泡抑素共同治疗可抵消这些作用。总之,我们对黑素细胞和黑素瘤细胞系中的激活素-激活素受体系统进行了表征,并发现黑素瘤细胞分泌的卵泡抑素可能是规避激活素负面调节作用的有效方法。

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