TY - JOUR
T1 - Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors
AU - Akino, Tomoshige
AU - Hida, Kyoko
AU - Hida, Yasuhiro
AU - Tsuchiya, Kunihiko
AU - Freedman, Deborah
AU - Muraki, Chikara
AU - Ohga, Noritaka
AU - Matsuda, Kouhei
AU - Akiyama, Kousuke
AU - Harabayashi, Toru
AU - Shinohara, Nobuo
AU - Nonomura, Katsuya
AU - Klagsbrun, Michael
AU - Shindoh, Masanobu
PY - 2009
Y1 - 2009
N2 - 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 tumorassociated 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 tumorstromal interactions.
AB - 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 tumorassociated 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 tumorstromal interactions.
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U2 - 10.2353/ajpath.2009.090202
DO - 10.2353/ajpath.2009.090202
M3 - Article
AN - SCOPUS:73549104498
SN - 0002-9440
VL - 175
SP - 2657
EP - 2667
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -