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

Histopathology. 2011 Jun;58(7):1096-106. doi: 10.1111/j.1365-2559.2011.03842.x.

Abstract

Aims: 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.

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 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.

MeSH terms

  • Antigens, CD34 / metabolism
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary*
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibroblasts / ultrastructure
  • Humans
  • Mast Cells / enzymology
  • Mast Cells / pathology*
  • Middle Aged
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Myocytes, Smooth Muscle / ultrastructure
  • Tryptases / metabolism*

Substances

  • Antigens, CD34
  • Tryptases