Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors

被引:153
作者
Akino, Tomoshige [2 ,3 ]
Hida, Kyoko [1 ,2 ]
Hida, Yasuhiro [4 ]
Tsuchiya, Kunihiko [2 ,3 ]
Freedman, Deborah [5 ,6 ]
Muraki, Chikara [2 ]
Ohga, Noritaka [2 ]
Matsuda, Kouhei [2 ]
Akiyama, Kousuke [2 ]
Harabayashi, Toru [3 ]
Shinohara, Nobuo [3 ]
Nonomura, Katsuya [3 ]
Klagsbrun, Michael [5 ]
Shindoh, Masanobu [2 ]
机构
[1] Hokkaido Univ, Div Vasc Biol, Grad Sch Dent Med, Kita Ku, Sapporo, Hokkaido 0608586, Japan
[2] Hokkaido Univ, Div Oral Pathobiol Sci, Grad Sch Dent Med, Sapporo, Hokkaido 0608586, Japan
[3] Hokkaido Univ, Grad Sch Med, Dept Renal & Genitourinary Surg, Sapporo, Hokkaido 0608586, Japan
[4] Hokkaido Univ, Grad Sch Med, Dept Surg Oncol, Sapporo, Hokkaido 0608586, Japan
[5] Harvard Univ, Childrens Hosp, Sch Med, Vasc Biol Program, Boston, MA 02115 USA
[6] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA
关键词
PHASE-III TRIAL; PROGENITOR CELLS; BREAST-CANCER; HEMATOPOIETIC STEM; ANGIOGENESIS; CARCINOMA; STROMA; THERAPY; GROWTH; GENES;
D O I
10.2353/ajpath.2009.090202
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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)
引用
收藏
页码:2657 / 2667
页数:11
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