The LIM-domain protein Lmo2 is a key regulator of tumour angiogenesis: a new anti-angiogenesis drug target.
The growth of solid tumours requires a blood supply provided by re-modeling of existing blood vessel endothelium (angiogenesis). Little is known about transcription regulators which are specific for the control of tumour angiogenesis. The proto-oncogene LMO2 encodes a LIM domain transcription regulator which controls angiogenesis during mouse embryogenesis where it regulates remodelling of the capillary network into mature vessels. We now show that Lmo2 expression is augmented in tumour endothelium such as mouse thymomas and human lung tumours. The functional significance of this Lmo2 expression was assessed in teratocarcinomas induced in nude mice by subcutaneous implantation of Lmo2-lacZ targeted ES cells. CD31-positive, sprouting endothelium of ES-cell origin occurred in teratocarcinomas from heterozygous Lmo2-lacZ ES cells but none occurred from null Lmo2-lacZ ES cells. Therefore, in this model Lmo2 is an obligatory regulator of neo-vascularization of tumours. These data suggest that LMO2 function may be a drug target in cancer and other conditions characterized by neo-vascularization.
Yamada
Yoshihiro
Y
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Pannell
Richard
R
Forster
Alan
A
Rabbitts
Terence H
TH
D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D015672:Erythroid Precursor Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008667:Metalloproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D013953:Thymus Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D001616:beta-Galactosidase
D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; C000715470:MAS1 protein, human; D008667:Metalloproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D001616:beta-Galactosidase