P2-05-03: Is Breast Cancer Tryptase a Novel Anti-Angiogenetic Molecular Target?

Abstract

Abstract Tryptase, a serine protease stored and released from mast cells granules has been identified as a new non-classical angiogenetic factor. Tryptase is an agonist of proteinase-activated receptor-2 a G protein involved in cellular proliferation and angiogenesis. On the other hand mast cells can release tryptase following c-Kit receptor activation. We have evaluated the correlations among the number of MCs positive to tryptase (MCDPT), the number of c-Kit receptor expressing cells (C-KREC) and microvascular density (MVD) in a series of 91 primary T1-3, N0-2 M0 female breast cancer by means of immunohistochemistry and image analysis methods. Six-micrometers thick serial sections of formalin-fixed and paraffin-embedded bioptic tumor samples were microwaved at 500 W for 10 min. and treated with a 3% hydrogen peroxide solution. Sections were incubated with primary antibodies: anti-tryptase (AA1; Dako, Glostrup, Denmark), anti-c-Kit receptor (A4502; Dako, Glostrup, Denmark) and anti-CD34 (QB-END 10; Bio-Optica Milan, Italy). In serial sections MVD, MCDPT and C-KREC were counted by means of image analysis (Quantimet 500 Leica) at x400 microscopic fields. Data demonstrated a significantly (r= ranging from 0.72 to 0.91; p: ranging from 0.001 to 0.003 by Pearson's analysis respectively) correlation between MVD, MCDPT and C-KREC to each other. Published in vitro data suggest that tryptase induce angiogenesis in vascular endothelial cells and breast cancer cells lines. According to these data we shown that MVD, MCDPT and C-KREC paralleled to each other suggesting a role in in vivo breast cancer angiogenesis. In this context the inhibition of c-Kit mast cells tryptase degranulation by several tyrosin kinase inhibitors might be evaluated in clinical trials. Finally available tryptase inhibitors such as gabexate mesilate or nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-03.