Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins
Related Experiment Video
Updated: Jul 15, 2026

Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
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.
Abstract:
Inhibition of alphavbeta3 or alphavbeta5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Here we report that mice lacking beta3 integrins or both beta3 and beta5 integrins not only support tumorigenesis, but have enhanced tumor growth as well. Moreover, the tumors in these integrin-deficient mice display enhanced angiogenesis, strongly suggesting that neither beta3 nor beta5 integrins are essential for neovascularization. We also observed that angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF) are augmented significantly in the absence of beta3 integrins. We found no evidence that the expression or functions of other integrins were altered as a consequence of the beta3 deficiency, but we did observe elevated levels of VEGF receptor-2 (also called Flk-1) in beta3-null endothelial cells. These data indicate that alphavbeta3 and alphavbeta5 integrins are not essential for vascular development or pathological angiogenesis and highlight the need for further evaluation of the mechanisms of action of alphav-integrin antagonists in anti-angiogenic therapeutics.
Insights
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.
Related Concept Videos
Mechanism of Angiogenesis
Regulation of Angiogenesis and Blood Supply
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Some...

