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Publications of the month

April 2011

Clinical and functional significance of α9β1 integrin expression in breast cancer: a novel cell-surface marker of the basal phenotype that promotes tumour cell invasion.

Allen MD, Vaziri R, Green M, Chelala C, Brentnall AR, Dreger S, Vallath S, Nitch-Smith H, Hayward J, Carpenter R, Holliday DL, Walker RA, Hart IR, Jones JL.
J Pathol. 2011 Apr;223(5):646-58. doi: 10.1002/path.2833. Epub 2011 Feb 21.

Fig_1a_Normal_Duc_Aprilt
Normal breast acinus,
Membrane staining localized to the myoepithelial layer of an acinus;
Magnification × 400

The aim of this study was to look at the expression of α9β1 integrin in normal and cancer breast tissues and examine how this might relate to patient survival. We found that the expression of α9β1 integrin:

  • Is a novel marker of the most aggressive form of breast cancer (the basal subtype of breast cancer), which has limited treatment options.
  • Is associated with reduced patient survival.
  • Promotes breast cancer cell invasion, thereby possibly contributing to the aggressive behaviour of the basal cancer phenotype.

 

Integrins, such as α9β1, are able to control important processes like cell growth, migration and survival, all key targets in the transformation of a normal cell to a cancer cell.  Similarly, changes in the microenvironment around cells - the extracellular matrix (ECM) - also influences many aspects of normal and cancer cell behaviour.

In breast cancer, there are changes in the presence and types of proteins making up the ECM (such as Fibronectin and Tenascin), which in turn influence the expression of integrins. 

In our study, we found that Tenascin and a certain type of fibronectin (called EDA) bind to a9b1, resulting in the activation and production of other proteins (e.g. TGF-b,   VEGF), which are involved in the process of new blood vessel growth (angiogenesis).  The production of new blood vessels is essential for the continued growth of a cancer and its spread (metastasis) to other sites in the body. 

For breast cancer patients, it is these metastases that result in the poorest prognosis, so it is important for us to understand the process to enable us to know how to control it.

Our study is one of the first to identify a function for a molecule in the basal-subtype of breast cancers. The work also emphasizes the importance of changes to the surrounding normal tissue in determining breast cancer behaviour.

Article by Dr Mike Allen
Postdoctoral Research Fellow
Centre for Tumour Biology

Fig_1b_DCIS_April

A duct showing features of ductal carcinoma in situ retains expression of α9β1 on the myoepithelial cell layer.
Staining of lymphovascular spaces for α9β1 is also evident;
Magnification × 200

Fig_1_c_Invasive_Ductal._Apriljpg

Grade 3 infiltrating ductal carcinoma
Showing strong and homogeneous diffuse cytoplasmic and membranous staining for α9β1;

Magnification × 200