Mediators of vascular remodelling co-opted for sequential steps in lung metastasis

Gaorav P. Gupta, Don X. Nguyen, Anne C. Chiang, Paula D. Bos, Juliet Y. Kim, Cristina Nadal, Roger R. Gomis, Katia Manova-Todorova and Joan Massagué ()
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Gaorav P. Gupta: Cancer Biology and Genetics Program,
Don X. Nguyen: Cancer Biology and Genetics Program,
Anne C. Chiang: Cancer Biology and Genetics Program,
Paula D. Bos: Cancer Biology and Genetics Program,
Juliet Y. Kim: Cancer Biology and Genetics Program,
Cristina Nadal: Cancer Biology and Genetics Program,
Roger R. Gomis: Cancer Biology and Genetics Program,
Katia Manova-Todorova: Molecular Cytology Core Facility, and,
Joan Massagué: Cancer Biology and Genetics Program,

Nature, 2007, vol. 446, issue 7137, 765-770

Abstract: Abstract Metastasis entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. Using genetic and pharmacological approaches, we show that the epidermal growth factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix metalloproteinases 1 and 2, when expressed in human breast cancer cells, collectively facilitate the assembly of new tumour blood vessels, the release of tumour cells into the circulation, and the breaching of lung capillaries by circulating tumour cells to seed pulmonary metastasis. These findings reveal how aggressive primary tumorigenic functions can be mechanistically coupled to greater lung metastatic potential, and how such biological activities may be therapeutically targeted with specific drug combinations.

Date: 2007
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DOI: 10.1038/nature05760

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