Sustained expression of homeobox D10 inhibits angiogenesis.
Homeobox (Hox) genes are master regulatory genes that direct organogenesis and maintain differentiated tissue function. As HoxD3 and HoxB3 promote angiogenesis, we investigated whether endothelial cells use other Hox genes to maintain a mature quiescent phenotype. HoxD10 expression was higher in quiescent as compared to tumor-associated angiogenic endothelium. Microarray analysis of HoxD10-overexpressing endothelial cells revealed a pattern of gene expression consistent with a nonangiogenic phenotype. Moreover, sustained expression of HoxD10 impaired endothelial cell migration and blocked angiogenesis induced by basic fibroblast growth factor and vascular endothelial growth factor in the chick chorioallantoic membrane in vivo. HoxD10-overexpressing human endothelial cells also failed to form new vessels when implanted into immunocompromised mice. These results indicate a role for HoxD10 in maintaining a nonangiogenic state in the endothelium.
Myers
Connie
C
Surgical Research Laboratory, Department of Surgery, University of California at San Francisco, San Francisco, CA 94143, USA.
Charboneau
Aubri
A
Cheung
Irene
I
Hanks
Douglas
D
Boudreau
Nancy
N
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D017690:Cell Transplantation; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C072064:HOXD10 protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2