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

摘要

AIMS: Cancerogenesis is characterized by increase of differentiated myofibroblasts. Mast cells (MCs) exert powerful effects on fibroblasts through a variety of mediators. We investigated alpha-smooth-muscle actin (alpha-SMA(+) ) and CD34(+) fibroblasts, density of toluidine blue-stained (MCs-TB) and tryptase-immunolabelled MCs (MCs-Try) in 30 primary breast tumours. METHODS AND RESULTS: Tumour (T), peri-tumoral (PT) and non-tumoral (NT) tissue was 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 adjacent PT than T. Transition between NT, PT and T was marked by increasing alpha-SMA(+) fibroblasts and slow disappearance of CD34(+) stromal cells. In NT, CD34(+) fibroblasts correlated with 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 alpha-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 suggests that during breast cancer progression the MCs may contribute to stromal remodelling and differentiation of myofibroblasts, through tryptase released in stromal microenvironment.