Cancer du sein et micro-environnement tumoral: rôle de la protéase ...

IntroductionConsumption of meals rich in fat and carbohydrates is a major causative factor ofobesity, resulting in excessive white adipose tissue. An increase of adipose tissuemass results from combined hypertrophy of existing adipocytes (hypertrophicadipocytes) and adipogenic differentiation of precursor cells (adipocyte hyperplasia).A large amount of adipose tissues has been associated with poor prognosis forbreast cancer in obese postmenauposal women (Calle & Kaaks, 2004). Recently,clinical studies pointed out that obesity is a major risk factor for cancer (Renehan etal., 2008; van Kruijsdijk et al., 2009; Wright et al., 2007).Tumor progression has been recently recognized as the product of an evolvingcross talk between tumor cells and its surrounding supportive tissue, the tumorstroma (Mueller & Fusenig, 2004). Cancer cells interact dynamically with multiplenormal cell types such as fibroblast, infiltrating immune cells, endothelial cells andadipocytes within the context of extra-cellular matrix (Mueller & Fusenig, 2004). Of allthe cells present in themicroenvironment, adipocyte is probably the least wellstudied despite the fact that it corresponds to one of the most prominent cell type intissues such as breast and bone marrow (Wiseman & Werb, 2002). Until recently,adipocytes were mainly considered as an energy storage depot, but there is nowclear evidence pointing to the fat tissue as an endocrine organ that produceshormones,growth factors, cytokines, proteases and other molecules, anheterogeneous group of molecules included under the term of adipokines (Rajala &Scherer, 2003). Accordingly, the adipocyte is therefore an excellent candidate toinfluence tumor behaviour through heterotypic signalling processes and may prove tobe critical for tumor survival, growth, and metastasis.3