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

DiscussionOur results demonstrate that cath-D expression is up-regulated in human obesetissue. This up-regulation of cath-D expression in the VAT and SAT ofoverweight/obese patients is in consensus with our results in obese mice. Obesity ischaracterized by the increase of intracellular lipid accumulation which shows asignificant correlation with adipocyte differentiation. Terminally differentiatedadipocytes cannot divide. Hence, alterations in the number of fat cells within the bodymust be accomplished by the differentiation of preadipocytes, which act as arenewable source of adipocytes.Our data point out that cath-D expression increased gradually along with thedifferentiation of NIH-3T3F442A cells into mature adipocytes. The comparableincrease between mRNA and protein levels observed in NIH-3T3F442A cellssuggests that the overall increase in cath-D expression following differentiation maybe primarily due to an increase in transcription with little or no post-transcriptionalregulation. Interestingly, our findings further revealed that fully-differentiated NIH-3T3F442A adipocytes secrete pro-cath-D, suggesting its potential new function as anadipokine. A recent study analysing the secretome of adipocytes reported that cath-D is a secretory protein induced by insulin (Zhou et al., 2009). Similar up-regulation ofcath-D was observed during adipocyte conversion of primary culture of preadipocytesisolated from human sub-cutaneous adipose tissue. Most functional studies onadipocyte differentiation and function have been performed in the murine adipogenicNIH-3T3L1 and NIH-F442A cell lines and in genetically modified mice. However,there are fundamental differences in the lipoprotein metabolism of mouse and human(Prawitt et al., 2008). Therefore, it is important to investigate the regulation cath-Dexpression in human adipocytes as presented in this report. Our report highlights that9