Remodeling of the microenvironment by aggressive melanoma tumor cells
Remodeling of the microenvironment by aggressive melanoma tumor cells
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DOI：
10.1111/j.1749-6632.2003.tb03218.x
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Seftor, REB
中科院分区：
文献类型：
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作者：
Hendrix, MJC;Seftor, EA;Seftor, REB
由血管生成和/或血管生成事件形成的血液供应是肿瘤发展和进展的必要条件，涉及细胞与其微环境的合作相互作用。基于最近侵袭性黑色素瘤细胞对血管源性模仿的表征，特别是它们表达VE（血管内皮）-钙粘蛋白、TIE-1和EphA2的能力，目前的研究主要集中在这些细胞重塑微环境时沉积的分子信号上。实验方法利用转移性黑色素瘤细胞预处理的独特三维胶原基质，其中含有层粘连蛋白5 - γ - 2链富集的轨道，通过与特定基质金属蛋白酶（MMPs）的合作相互作用产生促迁移裂解片段。研究结果首次表明，经转移细胞预处理的胶原基质可诱导侵袭性较差的黑色素瘤细胞表达关键的血管生成/血管生成/基质重塑基因。用一种MMP抑制剂治疗侵袭性黑色素瘤细胞，抑制了这些肿瘤细胞中血管生成模拟相关基因，并消除了预处理基质对侵袭性差的黑色素瘤细胞的诱导作用。这些观察结果说明了微环境对黑色素瘤细胞表型的显著影响，并可能为肿瘤细胞可塑性和独特的治疗策略提供新的视角。
A necessity for development and tumor progression is a blood supply formed by vasculogenic and/or angiogenic events, involving the cooperative interactions of cells with their microenvironment. Based on the recent characterization of vasculogenic mimicry by aggressive melanoma cells, particularly their ability to express VE (vascular endothelial)-cadherin, TIE-1, and EphA2, current studies have focused on the molecular signals deposited by these cells as they remodel their microenvironment. The experimental approach utilizes unique three-dimensional collagen matrices preconditioned by metastatic melanoma cells, which contain laminin 5 gamma2 chain-enriched tracks with promigratory cleavage fragments produced by cooperative interactions with specific matrix metalloproteinases (MMPs). The results demonstrate that the collagen matrices preconditioned by the metastatic cells induce poorly aggressive melanoma cells to express, for the first time, key angiogenic/vasculogenic/matrix-remodeling genes. Treatment of aggressive melanoma cells with an MMP inhibitor resulted in the inhibition of vasculogenic mimicry-associated genes in these tumor cells and abrogation of the inductive effects of the preconditioned matrix on poorly aggressive melanoma cells. These observations illustrate the remarkable influence of the microenvironment on the phenotype of melanoma cells and may provide new perspectives on tumor cell plasticity and unique treatment strategies.