Adhesion and Integrins
Why we focus on Adhesion and Integrins
Cell adhesion to the extracellular-matrix and to other cells, via specialised receptors such as integrins (cell-matrix and cell-cell) and cadherins (cell-cell), is a fundamental necessity in the maintenance of normal tissue biology. In cancer, the inappropriate expression or activity of many of these receptors actively promotes cancer progression, which is why we focus on understanding this process with a view to identifying new, molecular therapeutic targets.
What we do
- We investigate dysfunctional adhesion in Chronic Lymphocytic Leukaemia (CLL) and the potential use of immuno-modulatory drugs, which correct the dysfunction, to improve therapy of CLL.
- We study integrins that regulate endothelial growth factors, specifically αvβ3 and αvβ5. The absence of αvβ3 and αvβ5 increases both blood vessel and tumour growth, and therapy with very low concentrations of αvβ3/αvβ5 inhibitors actually increases blood vessel growth and tumour development, suggesting caution in the use of integrin inhibitors in cancer treatment.
- We focus on the epithelial-specific integrin αvβ6 as therapeutic target for carcinoma because it is not expressed by most normal tissues but is upregulated on many carcinomas including breast, colon, lung, pancreas and cervix making it a novel therapeutic target. We have been the first to show that αvβ6 promoted invasion, in part, by regulating matrix-metalloproteinases (MMPs). Strong expression of αvβ6 correlates with very poor prognosis from breast cancer. The BCI αvβ6-specific peptide (A20FMDV2) is being developed for radio-imaging of human cancers.
Key Publications
- Morgan et al. Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion. Oncogene 2011; 30: 1422-35.
- da Silva et al. Endothelial alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF. Am J Pathol 2010; 177: 1534-48.
- Saha et al. High-resolution in vivo imaging of breast cancer by targeting the pro-invasive integrin alphavbeta6. J Path 2010; 222: 52-63.
- Reynolds et al. Stimulation of tumour growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med 2009; 15: 392-400.
- Ramsay et al. CLL T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest 2008; 118: 2427-37.
- Reynolds et al. alpha3beta1 integrin-controlled Smad7 regulates reepithelialization during wound healing in mice. J Clin Invest 2008; 118: 965-74.
Who does the research
→ Click here for BCI senior researchers working on adhesion and integrins.
Major Funders
- BBSRC
- Breast Cancer Campaign
- Cancer Research UK
- DebRA
- European Haematology Association
- MRC
- Pancreatic Cancer Research Fund
