Children's Hospital of Chicago Research Center, Northwestern University, Chicago, Illinois 60614-3394, USA.
Am J Pathol. 2012 Oct;181(4):1115-25. doi: 10.1016/j.ajpath.2012.07.013. Epub 2012 Aug 31.
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 distinction as a citation classic. Tumor cell vasculogenic mimicry (VM) refers to the plasticity of aggressive cancer cells forming de novo vascular networks, which thereby contribute to perfusion of rapidly growing tumors, transporting fluid from leaky vessels, and/or connecting with the constitutional endothelial-lined vasculature. The tumor cells capable of VM share a plastic, transendothelial phenotype, which may be induced by hypoxia. Since VM was introduced 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. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, and hypoxia-related signaling pathways, each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype.
1999 年，《美国病理学杂志》发表了一篇题为“人类黑色素瘤细胞在体内和体外形成血管通道：血管生成拟态”的文章，作者是 Maniotis 及其同事。这篇文章引发了多年的激烈争论，并被誉为引用经典。肿瘤细胞血管生成拟态（VM）是指侵袭性癌细胞形成新的血管网络的可塑性，从而有助于快速生长的肿瘤的灌注，从渗漏的血管中运输液体，和/或与固有内皮衬里的脉管系统连接。具有 VM 能力的肿瘤细胞具有可塑性的跨内皮表型，这可能是由缺氧诱导的。自从 VM 被引入黑色素瘤肿瘤灌注的新范例以来，许多研究都有了新的发现，阐明了支持各种肿瘤（包括癌、肉瘤、神经胶质瘤、星形细胞瘤和黑色素瘤）中 VM 的潜在分子途径。促进肿瘤细胞 VM 的功能可塑性的是与血管、干细胞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。
