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黑色素瘤中的血管生成

Angiogenesis in melanoma.

作者信息

Mahabeleshwar Ganapati H, Byzova Tatiana V

机构信息

Department of Molecular Cardiology, J.J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

出版信息

Semin Oncol. 2007 Dec;34(6):555-65. doi: 10.1053/j.seminoncol.2007.09.009.

Abstract

The process of angiogenesis is crucial for progression and metastasis of the majority of solid tumors including melanomas. The current review summarizes existing knowledge of the mechanisms of angiogenesis in melanoma, as well as current anti-angiogenic therapeutic strategies and their targets. We focus primarily on the role of key growth factors that are secreted by melanoma cells and known to trigger angiogenic responses, and their receptors as expressed on both endothelial and melanoma cells. Many of these growth factors function in synergy with receptors for extracellular matrix, integrins, and matrix metalloproteinases (MMPs). All of these systems of molecules are activated during major stages of angiogenesis such as endothelial migration, proliferation, and reorganization of surrounding extracellular matrix. The blockade of these molecules and their downstream pathways leads to inhibition of melanoma vascularization. Thus, these classes of molecules are essential for melanoma angiogenesis and, therefore, might serve as promising targets for therapeutic intervention. Many recently developed compounds targeting key pathways in angiogenesis are in their final stages of clinical trials.

摘要

血管生成过程对于包括黑色素瘤在内的大多数实体瘤的进展和转移至关重要。本综述总结了黑色素瘤血管生成机制的现有知识,以及当前的抗血管生成治疗策略及其靶点。我们主要关注黑色素瘤细胞分泌的、已知可触发血管生成反应的关键生长因子的作用,以及它们在内皮细胞和黑色素瘤细胞上表达的受体。这些生长因子中的许多与细胞外基质、整合素和基质金属蛋白酶(MMPs)的受体协同发挥作用。所有这些分子系统在血管生成的主要阶段如内皮细胞迁移、增殖和周围细胞外基质的重组过程中被激活。阻断这些分子及其下游途径会导致黑色素瘤血管化受到抑制。因此,这些分子类别对于黑色素瘤血管生成至关重要,因此可能成为有前景的治疗干预靶点。许多最近开发的针对血管生成关键途径的化合物正处于临床试验的最后阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af00/2365306/e3b1d3794b1d/nihms36506f1.jpg

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