Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain.
Hemangiomas are angiogenesis-dependent benign vascular tumors that can rupture and cause intracranial hemorrhages. We previously showed that the transcription factor homeobox A5 (HoxA5), which is absent in activated angiogenic endothelial cells can block angiogenesis. Here, we investigated whether restoring expression of HoxA5 blocks hemangioma growth by transplanting mouse hemangioendothelioma endothelial cells (EOMA) or HoxA5-expressing EOMA cells into the brains of mice. The EOMA cells induced brain hemangiomas characterized by large cystlike spaces lined by thin walls of endothelial cells surrounded by scant smooth muscle cells. When HoxA5-expressing EOMA cells were injected, lesion volumes were reduced between 5- and 20-fold compared with the EOMA control group (p < 0.05). Restoration of HoxA5 was associated with increased thrombospondin-2, which inhibits angiogenesis and reduced hypoxia-inducible factor 1alpha expression. These data suggest that restoring HoxA5 can attenuate experimental brain hemangioma development.
Zhu
Yiqian
Y
Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
Cuevas
Ileana C
IC
Gabriel
Rodney Allanigue
RA
Su
Hua
H
Nishimura
Stephen
S
Gao
Peng
P
Fields
Alexander
A
Hao
Qi
Q
Young
William L
WL
Yang
Guo-Yuan
GY
Boudreau
Nancy J
NJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006391:Hemangioma / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology* / Q000601:surgery; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D037102:Lectins; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection / Q000379:methods; D000099262:Thrombospondin 2
D000199:Actins; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D037102:Lectins; D010750:Phosphoproteins; D012333:RNA, Messenger; D019699:Thrombospondins; D014157:Transcription Factors; D000099262:Thrombospondin 2; C497443:Hif1a protein, mouse; C059637:Hoxa5 protein, mouse