Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors.
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.
Akino
Tomoshige
T
Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Kita-ku, Sapporo, Japan.
Hida
Kyoko
K
Hida
Yasuhiro
Y
Tsuchiya
Kunihiko
K
Freedman
Deborah
D
Muraki
Chikara
C
Ohga
Noritaka
N
Matsuda
Kouhei
K
Akiyama
Kousuke
K
Harabayashi
Toru
T
Shinohara
Nobuo
N
Nonomura
Katsuya
K
Klagsbrun
Michael
M
Shindoh
Masanobu
M
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000235:genetics*; D002469:Cell Separation; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics; D002869:Chromosome Aberrations; D042783:Endothelial Cells / Q000473:pathology*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010455:Peptides; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000071916:AC133 Antigen; D015703:Antigens, CD; D002868:Chromosomal Proteins, Non-Histone; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C068688:centromere protein E