文章：

血管生成模拟和肿瘤细胞可塑性：来自黑色素瘤的教训

Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma

原文发布日期：2003-06-01

DOI: 10.1038/nrc1092

类型: Review Article

开放获取: 否

要点：

1. The molecular 'signature' of aggressive melanoma cells is illustrative of an undifferentiated cell with a gene-expression profile that is similar to that of embryonic-like cells.
2. Vasculogenic mimicry describes the ability of aggressive melanoma cells to express endothelium-associated genes and form extracellular matrix (ECM)-rich vasculogenic-like networks in three-dimensional culture. These networks recapitulate embryonic vasculogenesis, and they have been detected in human aggressive tumours.
3. Vasculogenic mimicry in melanoma involves several signalling molecules that are also involved in embryonic vasculogenesis, including vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular carcinoma-A2 (EPHA2), phosphatidylinositol 3-kinase, focal adhesion kinase, matrix metalloproteinases and laminin 5 γ2-chain.
4. The biological implications of vasculogenic mimicry in vivo are unclear, but recent studies indicate that the formation of vasculogenic-like networks that are rich in laminin could serve as an intratumoral fluid-conducting meshwork.
5. Vasculogenic mimicry has been observed in non-melanoma tumour types, including carcinomas of the breast, prostate, ovary and lung, synoviosarcoma, rhabdomyosarcoma and phaeochromocytoma, and in cytotrophoblasts forming the placenta.
6. Endostatin, an angiogenesis inhibitor, abrogates endothelial-cell-driven angiogenesis, but not vasculogenic mimicry, in melanomas.
7. Identification of the pathways that regulate this undifferentiated, highly plastic phenotype could lead to the development of new therapeutic strategies for cancer.

要点翻译：

1. 侵袭性黑色素瘤细胞的分子“特征”表现为一种未分化细胞，其基因表达谱与类胚胎细胞相似。
2. 血管生成拟态描述了侵袭性黑色素瘤细胞在三维培养中表达内皮相关基因并形成富含细胞外基质的类血管网络的能力。这些网络重现了胚胎血管生成过程，并已在人类侵袭性肿瘤中检测到。
3. 黑色素瘤中的血管生成拟态涉及多种信号分子，这些分子也参与胚胎血管生成，包括血管内皮钙黏蛋白、促红细胞生成素产生性肝细胞癌-A2、磷脂酰肌醇3-激酶、黏着斑激酶、基质金属蛋白酶以及层粘连蛋白5γ2链。
4. 血管生成拟态在体内的生物学意义尚不明确，但近期研究表明，富含层粘连蛋白的类血管网络可能作为肿瘤内的液体传导网络。
5. 在非黑色素瘤肿瘤类型中也观察到了血管生成拟态现象，包括乳腺癌、前列腺癌、卵巢癌和肺癌、滑膜肉瘤、横纹肌肉瘤和嗜铬细胞瘤，以及形成胎盘的细胞滋养层细胞。
6. 内皮抑素作为一种血管生成抑制剂，能阻断内皮细胞驱动的血管生成，但对黑色素瘤的血管生成拟态无效。
7. 识别调控这种未分化、高可塑性表型的通路，可能为开发新的癌症治疗策略奠定基础。

英文摘要：

The gene-expression profile of aggressive cutaneous and uveal melanoma cells resembles that of an undifferentiated, embryonic-like cell. The plasticity of certain types of cancer cell could explain their ability to mimic the activities of endothelial cells and to participate in processes such as neovascularization and the formation of a fluid-conducting, matrix-rich meshwork. This ability has been termed 'vasculogenic mimicry'. How does vasculogenic mimicry contribute to tumour progression, and can it be targeted by therapeutic agents?

摘要翻译： 

侵袭性皮肤与葡萄膜黑色素瘤细胞的基因表达谱类似于未分化的胚胎样细胞。某些类型癌细胞的这种可塑性或可解释其为何能模拟内皮细胞活动，并参与新生血管化以及富含基质的导液网状结构形成。该能力被称为“血管生成拟态”。血管生成拟态如何促进肿瘤进展？其能否成为治疗靶点？

原文链接：

Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma