Tissue remodelling in breast cancer: human mast cell tryptase as an initiator of myofibroblast differentiation

International audienceAims: Cancerogenesis is characterized by increase of differentiated myofibroblasts. Mast cells (MCs) exert powerful effects on fibroblasts through a variety of mediators. We investigated α-SMA+ and CD34+ fibroblasts, density of toluidine blue-stained (MCs-TB) and tryptase-immunolabeled MCs (MCs-Try) in 30 primary breast tumors. Methods and results: tumor (T), peri-tumoral (PT) and non-tumoral (NT) tissues were studied by immunohistochemistry and electron microscopy. MCs-TB and MCs-Try increased gradually from NT, to PT and T and the comparison between the three compartments varied significantly. Degranulated MCs were present more significantly in NT and in adjacent PT than T. Transition between NT, PT and T was marked by increasing α-SMA+ fibroblasts and slow disappearance of CD34+ stromal cells. In NT, CD34+ fibroblasts correlated to low density both of MCs-TB and intact MCs-Try (p=0.0346 and p=0.0409, respectively). In T, the few preserved CD34+ fibroblasts were associated with low-density degranulated MCs-Try (p=0.0173). The α-SMA+ fibroblasts correlated with high-density of intact MCs-Try in PT, and with high density of degranulated MCs-Try in T (p=0.0289), also confirmed by ultrastructural analysis. Conclusions: This preliminary investigation suggest that during breast cancer progression the MCs may contribute to stromal remodelling and differentiation of myofibroblasts, through tryptase released in stromal microenvironment