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Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins
Louise E Reynolds1, Lorenza Wyder, Julie C Lively
1Cell Adhesion and Disease Laboratory, Richard Dimbleby Department, Imperial Cancer Research Fund, St. Thomas' Hospital, London, UK.
Nature Medicine
|January 12, 2002
Summary
Integrins alphavbeta3 and alphavbeta5 are not essential for tumor angiogenesis. Mice lacking these integrins showed enhanced tumor growth and blood vessel formation, challenging previous assumptions.
Area of Science:
- Integrin biology
- Cancer research
- Angiogenesis
Background:
- Integrins alphavbeta3 and alphavbeta5 were thought to be critical for neovascularization and tumor growth.
- Inhibition of these integrins was proposed as a therapeutic strategy for anti-angiogenesis.
Purpose of the Study:
- To investigate the role of beta3 and beta5 integrins in tumorigenesis and angiogenesis.
- To determine if these integrins are essential for pathological neovascularization.
Main Methods:
- Analysis of tumor growth and angiogenesis in mice genetically deficient in beta3 or beta3/beta5 integrins.
- Assessment of angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF).
- Evaluation of VEGF receptor-2 (Flk-1) levels in endothelial cells.
Main Results:
- Mice lacking beta3 or beta3/beta5 integrins exhibited supported tumorigenesis and enhanced tumor growth.
- Tumors in integrin-deficient mice displayed increased angiogenesis.
- Angiogenic responses to hypoxia and VEGF were augmented in beta3-deficient mice.
- Elevated VEGF receptor-2 (Flk-1) levels were observed in beta3-null endothelial cells.
Conclusions:
- Integrins alphavbeta3 and alphavbeta5 are not essential for vascular development or pathological angiogenesis.
- These findings suggest that alphav-integrin antagonists may not be effective anti-angiogenic therapeutics through these mechanisms.
- Further research is needed to understand the precise roles of these integrins in cancer and vascular biology.
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