(A) MMP11 promotes tumor cell proliferation at early stage of tumor development. Immunofluorescence staining shows increased percentage of Ki-67-positive cells in the tumors of 6-week-old PyMTTg; MMP11Tg mice (a), whereas tumors from 10-week-old PyMTTg; MMP11KO animals (b) have less proliferating cells compared with their respective controls; (B) Left panel: Western blot protein expression profiles of Insulin-like growth factor-binding protein 1 (IGFBP1) (a) and of components of its downstream IGF1/AKT/FoxO1 signaling pathway (b) reveal activation of this cascade in representative tumors from 6-week-old PyMTTg; MMP11Tg mice and its decrease in tumors from 10-week-old PyMTTg; MMP11KO animals as compared to their respective control animals. Right panel: quantification of the ratios of phosphorylated proteins to total level compared to wildtype are presented, n = 6–8 mice/group, data are expressed as mean ± SEM, * p < 0.05, ** p < 0.01, *** p < 0.001 (unpaired t-test).