title: Tissue remodelling in breast cancer: human mast cell tryptase as an initiator of myofibroblast differentiation.
abstract: OBJECTIVE
  Cancerogenesis is characterized by increase of differentiated myofibroblasts. Mast cells (MCs) exert powerful effects on fibroblasts through a variety of mediators. We investigated α-smooth-muscle actin (α-SMA(+) ) and CD34(+) fibroblasts, density of toluidine blue-stained (MCs-TB) and tryptase-immunolabelled MCs (MCs-Try) in 30 primary breast tumours.
  
  
  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 α-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 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 suggests that during breast cancer progression the MCs may contribute to stromal remodelling and differentiation of myofibroblasts, through tryptase released in stromal microenvironment.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Centre Giovanni Paolo II, University of Bari, Bari, Italy. a.mangia@oncologico.bari.it
authors.forename: Anita
authors.initials: A
authors.lastname: Mangia
authors.forename: Andrea
authors.initials: A
authors.lastname: Malfettone
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossi
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Girolamo
authors.initials: G
authors.lastname: Ranieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Simone
authors.forename: Leonardo
authors.initials: L
authors.lastname: Resta
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000556:secondary*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000556:secondary*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D053802:Tryptases / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D053802:Tryptases