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Tumor-associated endothelial cells with cytogenetic abnormalities
Kyoko Hida1, Yasuhiro Hida, Dhara N Amin
1Vascular Biology Program, Department of Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Research
|November 19, 2004
Summary
Tumor endothelial cells, crucial for tumor growth, were found to be genetically abnormal, unlike normal cells. These cytogenetic changes, including aneuploidy, occur within the tumor microenvironment.
Area of Science:
- Cancer Biology
- Cell Biology
- Genetics
Background:
- Tumor angiogenesis is vital for tumor progression and metastasis.
- Tumor blood vessels exhibit morphological and functional differences from normal vessels.
- Tumor endothelial cells were previously assumed to be genetically normal.
Purpose of the Study:
- To investigate potential genotypic alterations in tumor endothelial cells.
- To compare the cytogenetic status of tumor-derived endothelial cells with normal endothelial cells.
Main Methods:
- Isolation of mouse endothelial cells from human tumor xenografts (melanoma, liposarcoma) and normal tissues (skin, adipose).
- Characterization using endothelial cell markers (e.g., CD31).
- Cytogenetic analysis via fluorescence in situ hybridization (FISH) for aneuploidy, centrosome number, and chromosomal aberrations.
Main Results:
- Tumor endothelial cells exhibited aneuploidy and abnormal multiple centrosomes, unlike diploid normal cells.
- Cytogenetic abnormalities in tumor endothelial cells were heterogeneous and non-clonal.
- Aneuploidy increased with cell culture passage.
- FISH analysis of tumor sections confirmed endothelial cell aneuploidy.
Conclusions:
- Tumor endothelial cells can acquire cytogenetic abnormalities within the tumor microenvironment.
- These findings challenge the assumption of genetic normality in tumor endothelial cells.
- Cytogenetic instability may contribute to the abnormal phenotype of tumor vasculature.