Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors
Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors
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DOI：
10.2353/ajpath.2009.090202
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发表时间：
2009-12-01
影响因子：
6
通讯作者：
Shindoh, Masanobu
中科院分区：
文献类型：
--
作者：
Akino, Tomoshige;Hida, Kyoko;Shindoh, Masanobu
肿瘤血管被认为含有遗传正常和稳定的内皮细胞（EC），不像肿瘤细胞，通常显示遗传不稳定性。然而，在人类肿瘤相关EC（hTECs）在癌症中的染色体畸变尚未进行研究。在这里，我们从20人肾细胞癌中分离出TEC，并分析其细胞遗传学异常。用7号和8号染色体DNA探针通过荧光原位杂交分析分离的hTECs的非整倍体程度。在人肾细胞癌中，22-58%（中位数，33%）的未培养的hTEC是非整倍体，而正常EC是二倍体。然后使用从人上皮肿瘤的异种移植物分离的小鼠TEC（mTEC）研究支配TEC非整倍性的机制。为了研究祖细胞对mTEC中非整倍性的贡献，比较了CD 133（+）和CD 133（-）mTEC的非整倍性。CD 133 + mTECs比CD 133- mTECs更频繁地显示非整倍体。这是第一个报告显示hTECs的细胞遗传学异常的癌症，与传统的信念相反。因此，肿瘤血管中的细胞遗传学改变可能发生，并可能在改变肿瘤-基质相互作用中发挥重要作用。(Am J Pathol 2009，175：2657-2667; DOI：10.2353/ajpath.2009.090202）
Tumor blood vessels are thought to contain genetically normal and stable endothelial cells (ECs), unlike tumor cells, which typically display genetic instability. Yet, chromosomal aberration in human tumor-associated ECs (hTECs) in carcinoma has not yet been investigated. Here we isolated TECs from 20 human renal cell carcinomas and analyzed their cytogenetic abnormalities. The degree of aneuploidy was analyzed by fluorescence in situ hybridization using chromosome 7 and chromosome 8 DNA probes in isolated hTECs. In human renal cell carcinomas, 22-58% (median, 33%) of uncultured hTECs were aneuploid, whereas normal ECs were diploid. The mechanisms governing TEC aneuploidy were then studied using mouse TECs (mTECs) isolated from xenografts of human epithelial tumors. To investigate the contribution of progenitor cells to aneuploidy in mTECs, CD133(+) and CD133(-) mTECs were compared for aneuploidy. CD133+ mTECs showed aneuploidy more frequently than CD133- mTECs. This is the first report showing cytogenetic abnormality of hTECs in carcinoma, contrary to traditional belief. Cytogenetic alterations in tumor vessels of carcinoma therefore can occur and may play a significant role in modifying tumor-stromal interactions. (Am J Pathol 2009, 175:2657-2667; DOI: 10.2353/ajpath.2009.090202)