Tumor-associated endothelial cells with cytogenetic abnormalities
Tumor-associated endothelial cells with cytogenetic abnormalities
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DOI：
10.1158/0008-5472.can-04-1567
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发表时间：
2004-11-15
期刊：
影响因子：
11.2
通讯作者：
Klagsbrun, M
中科院分区：
文献类型：
--
作者：
Hida, K;Hida, Y;Klagsbrun, M
肿瘤血管生成是实体瘤进展和转移所必需的。肿瘤血管已被证明不同于正常对应物，例如，通过形态学的变化。肿瘤血管生成中的一个重要概念是肿瘤内皮细胞被认为是遗传正常的，尽管这些内皮细胞在结构和功能上是异常的。然而，我们假设，鉴于肿瘤和正常血管之间的表型差异，也可能存在基因型改变：从两种不同的人类肿瘤异种移植物（黑色素瘤和脂肪肉瘤）和两种正常内皮细胞中分离小鼠内皮细胞。细胞对应物，皮肤和脂肪。肿瘤相关内皮细胞表达典型的内皮细胞标志物，如CD31。它们具有相对较大的异质细胞核。出乎意料的是，肿瘤内皮细胞的细胞遗传学异常。荧光原位杂交（FISH）分析显示，新鲜分离的未培养的肿瘤内皮细胞为非整倍体，并有异常的多个中心体。非整倍体的程度加剧了在文化中的传代。多色荧光原位杂交结果显示，肿瘤内皮细胞染色体结构畸变具有异质性，表明细胞遗传学改变不是克隆性的。在小鼠肿瘤内皮细胞中没有人肿瘤源性染色体物质的证据。与此形成鲜明对比的是，新鲜分离的正常皮肤和脂肪内皮细胞是二倍体，具有正常的中心体，并且在培养中甚至在20代内保持细胞遗传学稳定。肿瘤切片的FISH分析也显示内皮细胞非整倍体。我们的结论是，肿瘤内皮细胞可以获得细胞遗传学异常，而在肿瘤微环境。
Tumor angiogenesis is necessary for solid tumor progression and metastasis. Tumor blood vessels have been shown to differ from normal counterparts, for example, by changes in morphology. An important concept in tumor angiogenesis is that tumor endothelial cells are assumed to be genetically normal, although these endothelial cells are structurally and functionally abnormal. However, we hypothesized that given the phenotypic differences between tumor and normal blood vessels, there may be genotypic alterations as well: Mouse endothelial cells were isolated from two different human tumor xenografts, melanoma and liposarcoma, and from two normal endothelial. cell counterparts, skin and adipose. Tumor-associated endothelial cells expressed typical endothelial cell markers, such as CD31. They had relatively large, heterogeneous nuclei. Unexpectedly, tumor endothelial cells were cytogenetically abnormal. Fluorescence in situ hybridization (FISH) analysis showed that freshly isolated uncultured tumor endothelial cells were aneuploid and had abnormal multiple centrosomes. The degree of aneuploidy was exacerbated by passage in culture. Multicolor FISH indicated that the structural chromosomal aberrations in tumor endothelial cells were heterogeneous, indicating that the cytogenetic alterations were not clonal. There was no evidence of human tumor-derived chromosomal material in the mouse tumor endothelial cells. In marked contrast, freshly isolated normal skin and adipose endothelial cells were diploid, had normal centrosomes, and remained cytogenetically stable in culture even up to 20 passages. FISH analysis of tumor sections also showed endothelial cell aneuploidy. We conclude that tumor endothelial cells can acquire cytogenetic abnormalities while in the tumor microenvironment.