Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.
Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.
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DOI：
10.1186/s12943-020-01288-1
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发表时间：
2021-01-04
期刊：
影响因子：
37.3
通讯作者：
Zeng Z
中科院分区：
文献类型：
--
作者：
Wei X;Chen Y;Jiang X;Peng M;Liu Y;Mo Y;Ren D;Hua Y;Yu B;Zhou Y;Liao Q;Wang H;Xiang B;Zhou M;Li X;Li G;Li Y;Xiong W;Zeng Z
血管生成模拟（vascular genic mimicry， VM）是近年来在许多恶性肿瘤中发现的一种血管生成过程，它不同于传统的血管生成过程涉及血管内皮。它涉及由肿瘤细胞组成的微血管通道的形成；因此，VM被认为是侵袭性肿瘤新血管形成的新模式，可以为肿瘤生长提供血液供应。许多研究指出，近年来一些临床治疗血管生成效果不理想可能与VM的激活有关。虽然VM的机制尚未完全阐明，但越来越多的土壤“微环境”对肿瘤生长的研究表明，实体肿瘤初始缺氧环境与VM密不可分。在这篇综述中，我们描述了在缺氧微环境下，癌症干细胞的干性和分化潜力通过缺氧诱导的上皮-内皮转化（EET）和细胞外基质（ECM）重塑而增强，形成血管生成模拟的特定机制；我们还总结了目前一些通过这些过程靶向VM的药物，为肿瘤血管生成的临床治疗提供新的参考。总的来说，VM抑制剂与传统的抗血管生成治疗联合使用是提高靶向血管生成治疗有效性的一种有希望的策略；此外，考虑到缺氧在肿瘤侵袭和转移中的重要性，靶向缺氧信号通路的药物似乎取得了良好的效果。
Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil “microenvironment” for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.
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