Molecular Pathways Molecular Pathways : Vasculogenic Mimicry in Tumor Cells : Diagnostic and Therapeutic Implications
Molecular Pathways Molecular Pathways : Vasculogenic Mimicry in Tumor Cells : Diagnostic and Therapeutic Implications
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发表时间：
2012
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通讯作者：
D. Kirschmann;E. Seftor;Katharine M. Hardy;Richard E. B. Seftor;M. Hendrix
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作者：
D. Kirschmann;E. Seftor;Katharine M. Hardy;Richard E. B. Seftor;M. Hendrix
肿瘤细胞血管生成拟态（VM）描述了侵袭性癌细胞形成从头血管网络的功能可塑性，从而为快速生长的肿瘤提供灌注途径，从泄漏的血管输送流体，和/或与内皮衬里的脉管系统连接。VM的潜在诱导似乎与缺氧有关，缺氧也可能促进能够VM的肿瘤细胞的可塑性、跨内皮表型。自1999年作为黑色素瘤肿瘤灌注的新范例引入以来，许多研究对支持各种肿瘤（包括黑色素瘤、胶质母细胞瘤、癌和肉瘤）中VM的潜在分子途径提供了新的见解。特别是，关键的VM调节基因与血管（VE-钙粘蛋白，EphA 2，VEGF受体1），胚胎和/或干细胞（Nodal，Notch 4），和缺氧相关（缺氧诱导因子，Twist 1）信号通路相关。这些途径中的每一个都值得认真审查，作为潜在的治疗、血管靶点和可塑性、耐药性和侵袭性转移表型的诊断指标。临床癌症研究; 18（10）; 1-7。2012年AACR。
Tumor cell vasculogenic mimicry (VM) describes the functional plasticity of aggressive cancer cells forming de novo vascular networks, thereby providing a perfusion pathway for rapidly growing tumors, transporting fluid from leaky vessels, and/or connecting with endothelial-lined vasculature. The underlying induction of VM seems to be related to hypoxia, which may also promote the plastic, transendothelial phenotype of tumor cells capable of VM. Since its introduction in 1999 as a novel paradigm for melanoma tumor perfusion, many studies have contributed new insights into the underlying molecular pathways supporting VM in a variety of tumors, including melanoma, glioblastoma, carcinomas, and sarcomas. In particular, critical VM-modulating genes are associated with vascular (VE-cadherin, EphA2, VEGF receptor 1), embryonic and/or stem cell (Nodal, Notch4), and hypoxia-related (hypoxia-inducible factor, Twist1) signaling pathways. Each of these pathways warrants serious scrutiny as potential therapeutic, vascular targets, and diagnostic indicators of plasticity, drug resistance, and the aggressive metastatic phenotype. Clin Cancer Res; 18(10); 1–7. 2012 AACR.