PMID- 15548691
OWN - NLM
STAT- MEDLINE
DCOM- 20050224
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 22
DP  - 2004 Nov 15
TI  - Tumor-associated endothelial cells with cytogenetic abnormalities.
PG  - 8249-55
AB  - Tumor angiogenesis is necessary for solid tumor progression and metastasis. Tumor 
      blood vessels have been shown to differ from normal counterparts, for example, by 
      changes in morphology. An important concept in tumor angiogenesis is that tumor 
      endothelial cells are assumed to be genetically normal, although these 
      endothelial cells are structurally and functionally abnormal. However, we 
      hypothesized that given the phenotypic differences between tumor and normal blood 
      vessels, there may be genotypic alterations as well. Mouse endothelial cells were 
      isolated from two different human tumor xenografts, melanoma and liposarcoma, and 
      from two normal endothelial cell counterparts, skin and adipose. Tumor-associated 
      endothelial cells expressed typical endothelial cell markers, such as CD31. They 
      had relatively large, heterogeneous nuclei. Unexpectedly, tumor endothelial cells 
      were cytogenetically abnormal. Fluorescence in situ hybridization (FISH) analysis 
      showed that freshly isolated uncultured tumor endothelial cells were aneuploid 
      and had abnormal multiple centrosomes. The degree of aneuploidy was exacerbated 
      by passage in culture. Multicolor FISH indicated that the structural chromosomal 
      aberrations in tumor endothelial cells were heterogeneous, indicating that the 
      cytogenetic alterations were not clonal. There was no evidence of human 
      tumor-derived chromosomal material in the mouse tumor endothelial cells. In 
      marked contrast, freshly isolated normal skin and adipose endothelial cells were 
      diploid, had normal centrosomes, and remained cytogenetically stable in culture 
      even up to 20 passages. FISH analysis of tumor sections also showed endothelial 
      cell aneuploidy. We conclude that tumor endothelial cells can acquire cytogenetic 
      abnormalities while in the tumor microenvironment.
FAU - Hida, Kyoko
AU  - Hida K
AD  - Vascular Biology Program, Department of Surgery, Children's Hospital and Harvard 
      Medical School, Boston, Massachusetts 02115, USA.
FAU - Hida, Yasuhiro
AU  - Hida Y
FAU - Amin, Dhara N
AU  - Amin DN
FAU - Flint, Alan F
AU  - Flint AF
FAU - Panigrahy, Dipak
AU  - Panigrahy D
FAU - Morton, Cynthia C
AU  - Morton CC
FAU - Klagsbrun, Michael
AU  - Klagsbrun M
LA  - eng
GR  - CA37392/CA/NCI NIH HHS/United States
GR  - CA45548/CA/NCI NIH HHS/United States
GR  - P30 CA06516/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA Primers)
SB  - IM
MH  - Aneuploidy
MH  - Animals
MH  - Base Sequence
MH  - Centrosome
MH  - *Chromosome Aberrations
MH  - DNA Primers
MH  - Endothelium, Vascular/*ultrastructure
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms, Experimental/*blood supply
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2004/11/19 09:00
MHDA- 2005/02/25 09:00
CRDT- 2004/11/19 09:00
PHST- 2004/11/19 09:00 [pubmed]
PHST- 2005/02/25 09:00 [medline]
PHST- 2004/11/19 09:00 [entrez]
AID - 64/22/8249 [pii]
AID - 10.1158/0008-5472.CAN-04-1567 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Nov 15;64(22):8249-55. doi: 10.1158/0008-5472.CAN-04-1567.