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The LIM-domain protein Lmo2 is a key regulator of tumour angiogenesis: a new anti-angiogenesis drug target

Oncogene volume 21, pages 1309–1315 (2002)Cite this article

Abstract

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.

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Acknowledgements

We would like to thank Matt McCormack for discussions during this work and Gareth King, Theresa Langford, Angela Middleton and Tina Hamilton for expert help. Y Yamada was generously supported by an award from the National Foundation for Cancer Research, USA. We also wish to thank Peter Goldstraw for the lung tumour biopsies used in this work.

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Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH1, UK

    Yoshihiro Yamada, Richard Pannell, Alan Forster & Terence H Rabbitts

  2. Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan

    Yoshihiro Yamada

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  1. Yoshihiro Yamada
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  2. Richard Pannell
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  3. Alan Forster
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  4. Terence H Rabbitts
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Correspondence to Terence H Rabbitts.

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Yamada, Y., Pannell, R., Forster, A. et al. The LIM-domain protein Lmo2 is a key regulator of tumour angiogenesis: a new anti-angiogenesis drug target. Oncogene 21, 1309–1315 (2002). https://doi.org/10.1038/sj.onc.1205285

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