Nodal as a biomarker for melanoma progression and a new therapeutic target for clinical intervention.
Nodal as a biomarker for melanoma progression and a new therapeutic target for clinical intervention.
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DOI：
10.1586/17469872.4.1.67
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Hendrix MJ
中科院分区：
文献类型：
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作者：
Strizzi L;Postovit LM;Margaryan NV;Lipavsky A;Gadiot J;Blank C;Seftor RE;Seftor EA;Hendrix MJ
Nodal 是一种胚胎形态发生素，属于 TGF-β 超家族，是胚胎干细胞命运的重要调节因子。我们最近证明 Nodal 在侵袭性黑色素瘤中显着表达。令人惊讶的是，仅在一小部分黑色素瘤肿瘤细胞群中检测到了 Nodal 辅助受体 Cripto-1 的表达，这表明 Nodal 的独立于 Cripto-1 的信号传导在黑色素瘤中发挥着主要作用。在这篇综述中，我们讨论了胚胎环境中存在的调节因子（例如 Lefty）如何下调 Nodal 表达并抑制黑色素瘤细胞的致瘤性和可塑性。我们的转化研究表明，在体内肺定植测定中，针对 Nodal 的抗体能够抑制黑色素瘤血管生成拟态并诱导黑色素瘤肿瘤细胞凋亡。我们之前的工作和正在进行的研究表明，Nodal 可能代表黑色素瘤的一种新型诊断标记物和治疗靶点。
Nodal, an embryonic morphogen belonging to the TGF-β superfamily, is an important regulator of embryonic stem cell fate. We have recently demonstrated that Nodal is expressed significantly in aggressive melanoma. Surprisingly, expression of the Nodal coreceptor, Cripto-1, was detected in only a small fraction of the melanoma tumor cell population, indicating a primary role for Cripto-1-independent signaling of Nodal in melanoma. In this review, we discuss how regulatory factors present in an embryonic environment, such as Lefty, can downregulate Nodal expression and inhibit tumorigenicity and plasticity of melanoma cells. Our translational studies show that antibodies against Nodal are capable of repressing melanoma vasculogenic mimicry and of inducing apoptosis in melanoma tumors in an in vivo lung-colonization assay. Our previous work and ongoing studies suggest that Nodal may represent a novel diagnostic marker and therapeutic target in melanoma.