Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors

Tomoshige Akino, Kyoko Hida, Yasuhiro Hida, Kunihiko Tsuchiya, Deborah Freedman, Chikara Muraki, Noritaka Ohga, Kouhei Matsuda, Kousuke Akiyama, Toru Harabayashi, Nobuo Shinohara, Katsuya Nonomura, Michael Klagsbrun, Masanobu Shindoh

Research output: Contribution to journalArticlepeer-review

171 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2657-2667
Number of pages11
JournalAmerican Journal of Pathology
Volume175
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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