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

The aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breastcancer (Ferrandina et al., 1997; Foekens et al., 1999; Rochefort, 1992; Rodriguez etal., 2005; Westley & May, 1999), is overexpressed and secreted at high levels byhuman epithelial breast cancer cells (Capony et al., 1987; Capony et al., 1989;Liaudet-Coopman et al., 2006; Rochefort & Liaudet-Coopman, 1999; Westley &Rochefort, 1980). Cath-D stimulates cancer cell proliferation, fibroblast outgrowth,angiogenesis and metastasis (Berchem et al., 2002; Fusek & Vetvicka, 1994; Garciaet al., 1990; Glondu et al., 2001; Glondu et al., 2002; Hu et al., 2008; Laurent-Mathaet al., 2005; Liaudet et al., 1995; Liaudet et al., 1994). Here, we investigated theexpression of cath-D in obese adipocytes and its role in the control of adipogenesis.We show that cath-D expression is up-regulated in human and mouse obese adiposetissues as well as during adipogenesis. Moreover, we demonstrate that cath-Dpositively controls the adipogenic process.ResultsCath-D transcription is up-regulated in human and mouse obese adiposetissuesBecause of the recently established relationship between obesity and cancerincidence (Renehan et al., 2008; van Kruijsdijk et al., 2009; Wright et al., 2007) andof the demonstrated role of cath-D in both cancer cells and stromal cells (Liaudet-Coopman et al., 2006), we investigated cath-D expression in human and mouseadipose tissues.Cath-D mRNA expression was examined in human intra-abdominal visceraladipose tissue (VAT) from lean and obese human (Fig. 1A, panel a). Interestingly,cath-D mRNA was significantly increased in human obese visceral adipose tissue4