Tumor cell vascular mimicry: Novel targeting opportunity in melanoma.
Tumor cell vascular mimicry: Novel targeting opportunity in melanoma.
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DOI：
10.1016/j.pharmthera.2016.01.006
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发表时间：
2016-03
影响因子：
13.5
通讯作者：
Chu YW
中科院分区：
文献类型：
--
作者：
Hendrix MJ;Seftor EA;Seftor RE;Chao JT;Chien DS;Chu YW
1999年，《美国病理学杂志》发表了一篇由Maniotis及其同事撰写的题为《人黑色素瘤细胞在体内和体外形成血管通道：血管生成模仿》的文章，引发了数年的激烈辩论，并为该杂志赢得了“引用经典”的称号。肿瘤细胞血管生成模仿（VM），也称为血管模仿，描述了侵袭性癌细胞形成新生血管网络的可塑性，并与恶性表型和不良临床结果相关。能够VM的肿瘤细胞具有干细胞样、跨内皮表型的共性，这可能是由缺氧诱导的。自从它作为黑色素瘤肿瘤灌注的新范例被引入以来，许多研究已经提供了新的发现，阐明了支持VM在各种肿瘤中的潜在分子途径，包括癌、肉瘤、胶质母细胞瘤、星形细胞瘤和黑色素瘤。特别重要的是血管生成抑制剂对肿瘤细胞VM缺乏有效性，这表明这种表型对常规治疗有选择性抵抗。促进肿瘤细胞功能可塑性的VM是与血管、干细胞、细胞外基质和缺氧相关信号通路相关的关键蛋白，每一个都值得认真考虑作为潜在的治疗靶点和侵袭性、转移性表型的诊断指标。本文综述了与VM相关的重要发现，包括目前正在临床开发的一种新型小分子化合物CVM-1118对VM的作用，并以黑色素瘤为模型，阐明了参与抑制这种可塑性侵袭性表型的重要分子途径。
In 1999, the American Journal of Pathology published an article, entitled “Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry” by Maniotis and colleagues, which ignited a spirited debate for several years and earned the journal's distinction of a “citation classic”. Tumor cell vasculogenic mimicry (VM), also known as vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. The tumor cells capable of VM share the commonality of a stem cell-like, transendothelial phenotype, which may be induced by hypoxia. Since its introduction as a novel paradigm for melanoma tumor perfusion, many studies have contributed new findings illuminating the underlying molecular pathways supporting VM in a variety of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas, and melanomas. Of special significance is the lack of effectiveness of angiogenesis inhibitors on tumor cell VM, suggesting a selective resistance by this phenotype to conventional therapy. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, extracellular matrix, and hypoxia-related signaling pathways -- each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype. This review highlights seminal findings pertinent to VM, including the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model.