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**10** 

*Canada* 

**Hyaluronan Associated Inflammation** 

**Influences Breast Cancer Progression** 

**and Microenvironment Remodelling** 

*1London Regional Cancer Program, London Health Sciences Center,* 

Caitlin Ward1, Catalina Vasquez1,2, Cornelia Tolg1,3,

*2Dept. of Medical Biophysics University of Western Ontario* 

*4Dept. of Oncology, University of Western Ontario, London ON 5Dept. of Biochemistry, University of Western Ontario, London ON* 

The breast is an organ composed predominantly of glandular, fatty, and fibrous tissues. Glandular tissue is composed of ducts lined by luminal epithelial cells that secrete milk, and is surrounded by a layer of myoepithelial cells that contract to release milk. Myoepithelial cells produce proteases, growth factors and growth factor receptors that contribute to remodelling during breast tissue expansion. Each duct is enclosed by a laminin-rich basement membrane and embedded in extracellular matrix (ECM). Mammary gland ECM and is a mixture of fibrillar proteins such as collagens, laminins, fibronectin, and polysaccharides such as heparin sulphate, chondroitin sulphate and hyaluronan (HA). These collectively provide the mechanical and structural support required for maintaining mammary tissue architecture and for storage of the soluble regulatory molecules needed for tissue homeostasis, plasticity, and remodelling. ECM promotes both the differentiated, homeostatic integrity of mammary tissue and is also a key determinant in branching morphogenesis, response-to-injury and pathological processes such as neoplastic disease. The importance of the ECM in determining homeostatic vs. tumourigenic events was originally demonstrated three decades ago by Beatrice Mintz, who showed that marked embryonic carcinoma cells injected into blastocysts do not give rise to tumours but instead contribute to normal tissue architecture. The same cells injected into adult mice develop into tumours (Mintz and Illmensee, 1975). Components of the microenvironment that support tumour progression have since been identified. For example, chick embryos infected with Rous Sarcoma virus express the oncogene v-src in every cell but tumours develop only at sites of wounding

due to the accumulation of TGF-β1 (Weigelt and Bissell, 2008).

**1. Introduction** 

**1.1 The breast microenvironment** 

Patrick G. Telmer1 and Eva Turley1,4,5

*3The Hospital for Sick Children, Toronto ON* 

*Victoria Hospital, London ON* 

