Genes that distinguish physiological and pathological angiogenesis.
To unravel the normal vasculature transcriptome and determine how it is altered by neighboring malignant cells, we compared gene expression patterns of endothelial cells derived from the blood vessels of eight normal resting tissues, five tumors, and regenerating liver. Organ-specific endothelial genes were readily identified, including 27 from brain. We also identified 25 transcripts overexpressed in tumor versus normal endothelium, including 13 that were not found in the angiogenic endothelium of regenerating liver. Most of the shared angiogenesis genes have expected roles in cell-cycle control, but those specific for tumor endothelium were primarily cell surface molecules of uncertain function. These studies reveal striking differences between physiological and pathological angiogenesis potentially important for the development of tumor-specific, vascular-targeted therapies.
Seaman
Steven
S
Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Stevens
Janine
J
Yang
Mi Young
MY
Logsdon
Daniel
D
Graff-Cherry
Cari
C
St Croix
Brad
B
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D060887:B7 Antigens; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000378:metabolism; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008115:Liver Regeneration; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009928:Organ Specificity; D011971:Receptors, Immunologic / Q000378:metabolism
D015703:Antigens, CD; D060887:B7 Antigens; D014408:Biomarkers, Tumor; C423237:CD276 protein, human; D011971:Receptors, Immunologic