Journal
JOURNAL OF PATHOLOGY
Volume 223, Issue 5, Pages 646-658Publisher
WILEY-BLACKWELL
DOI: 10.1002/path.2833
Keywords
integrin; breast cancer; basal phenotype; survival; invasion
Funding
- Barts and the London Charitable Foundation [472/685]
- Pathological Society of Great Britain and Ireland
- Cancer Research UK [12008] Funding Source: researchfish
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Integrin alpha 9 beta 1 is a receptor for ECM proteins, including Tenascin-C and the EDA domain of fibronectin, and has been shown to transduce TGF beta signalling. This study has examined the expression pattern of alpha 9 beta 1 in 141 frozen breast carcinoma samples and related expression to prognostic indices, molecular subtype and patient outcome. Effects of alpha 9 beta 1 on tumour cell migration and invasion were assessed using blocking antibody and gene transduction approaches. Integrin alpha 9 beta 1 localized to myoepithelial cells in normal ducts and acini, a pattern maintained in DCIS. A subset (17%) of invasive carcinomas exhibited tumour cell expression of alpha 9 beta 1, which related significantly to the basal-like phenotype, as defined by either CK5/6 or CK14 expression. Tumour expression of alpha 9 beta 1 showed a significant association with reduced overall patient survival (p < 0.0001; HR 5.94, 95%CI 3.26-10.82) and with reduced distant-metastasis-free survival (p < 0.0001; HR 6.37, CI 3.51-11.58). A series of breast cancer cell lines was screened for alpha 9 beta 1 with the highly invasive basal-like GI-101 cell line expressing significant levels. Both migration and invasion of this line were reduced significantly in the presence of alpha 9-blocking antibody and following alpha 9-knockdown with siRNA. Conversely, migratory and invasive behaviour of alpha 9-negative MCF7 cells and alpha 9-low MDA MB468 cells was enhanced significantly by over-expression of alpha 9. Thus, alpha 9 beta 1 acts as a novel marker of the basal-like breast cancer subtype and expression is associated with reduced survival, while its ability to promote breast cancer cell migration and invasion suggests that it contributes to the aggressive clinical behaviour of this tumour subtype. Copyright. (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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