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PMID: 19875502 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The American journal of pathology ·Vol. 175 ·No. 6 ·2009-12-00 ·Pages 2657-67

Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Akiyama K, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M, Shindoh M

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 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.

MeSH Terms
AC133 Antigen Antigens, CD/biosynthesis Carcinoma, Renal Cell/blood supply,genetics Cell Separation Chromosomal Proteins, Non-Histone/biosynthesis,genetics Chromosome Aberrations Endothelial Cells/pathology Flow Cytometry Glycoproteins/biosynthesis Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kidney Neoplasms/blood supply,genetics Neovascularization, Pathologic/genetics Peptides Reverse Transcriptase Polymerase Chain Reaction
Chemicals
AC133 Antigen Antigens, CD Chromosomal Proteins, Non-Histone Glycoproteins PROM1 protein, human Peptides Prom1 protein, mouse centromere protein E
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Akino Tomoshige
Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo, Japan.
Hida Kyoko
Hida Yasuhiro
Tsuchiya Kunihiko
Freedman Deborah
Muraki Chikara
Ohga Noritaka
Matsuda Kouhei
Akiyama Kousuke
Harabayashi Toru
Shinohara Nobuo
Nonomura Katsuya
Klagsbrun Michael
Shindoh Masanobu
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
1525-2191
DOI
10.2353/ajpath.2009.090202
Published
2009-12-00
Epub
2009-00-29
Pages
2657-67
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC2789618
Subset
IM
External Links
PubMed source DOI: 10.2353/ajpath.2009.090202 PMC Full Text View journal details
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