Integrins in cancer: biological implications and therapeutic opportunities
Top Cited Papers
- 1 January 2010
- journal article
- review article
- Published by Springer Nature in Nature Reviews Cancer
- Vol. 10 (1), 9-22
- https://doi.org/10.1038/nrc2748
Abstract
Integrin signalling regulates diverse functions in tumour cells, including migration, invasion, proliferation and survival. In several tumour types, the expression of particular integrins correlates with increased disease progression and decreased patient survival. In addition to tumour cells, integrins are also found on tumour-associated host cells, such as the vascular endothelium, perivascular cells, fibroblasts, bone marrow-derived cells and platelets. Integrin signalling crucially regulates the contribution of these cell types to cancer progression. Therefore, integrin antagonists may inhibit tumour progression by blocking crucial signalling events in both the tumour microenvironment and the tumour cells themselves. Integrins have a profound influence on tumour cells, both in the ligated and unligated states, in which they regulate tumour cell survival and malignancy. Although integrins alone are not oncogenic, recent data have found that some oncogenes may require integrin signalling for their ability to initiate tumour growth and invasion. These effects may be due to the important contribution of integrin signalling in maintaining the cancer stem cell population in a given tumour. Crosstalk between integrins and growth factor or cytokine receptors on both tumour and host cell types is vital for many aspects of tumour progression. Mechanisms of crosstalk include both direct and indirect association of integrins with growth factor or cytokine receptors, which affects the expression, ligand affinity and signalling of the receptors. The important contribution of integrins to the biology of both tumour cells and tumour-associated cell types has made them appealing targets for the design of specific therapeutics. Of particular interest, the integrin αv inhibitor cilengitide is now in a Phase III clinical trial in glioblastoma, and because this is the first integrin antagonist to achieve this milestone it places anti-integrin therapy on the doorstep of clinical availability. In addition to their use as therapeutic targets, integrins can be imaging biomarkers for assessing the efficacy of anti-angiogenic and anti-tumour agents. Integrin-targeted nanoparticles with a diverse array of anti-tumour payloads also represent a particularly promising area of research that may decrease the toxicities associated with systemic delivery of radiation or chemotherapy.Keywords
This publication has 195 references indexed in Scilit:
- An integrin αvβ3–c-Src oncogenic unit promotes anchorage-independence and tumor progressionNature Medicine, 2009
- Intravascularly Administered RGD-Displaying Measles Viruses Bind to and Infect Neovessel Endothelial Cells In VivoMolecular Therapy, 2009
- Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant MetastasisCancer Cell, 2009
- A role for VEGF as a negative regulator of pericyte function and vessel maturationNature, 2008
- Growth control by intracellular tension and extracellular stiffnessTrends in Cell Biology, 2008
- Integrin-mediated laminin-1 adhesion upregulates CXCR4 and IL-8 expression in pancreatic cancer cellsSurgery, 2007
- Tumor microvasculature and microenvironment: Targets for anti-angiogenesis and normalizationMicrovascular Research, 2007
- β4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancerLaboratory Investigation, 2005
- Targeted disruption of β1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor inductionCancer Cell, 2004
- Anoikis mechanismsCurrent Opinion in Cell Biology, 2001