Figure 4

Effects of TGF-β antagonists on experimental MDA-MB-231 human breast cancer cell metastases in vivo. A. Mice were inoculated with bone-tropic SCP2TR cells via intracardiac injection and treated with vehicle, 13C4 isotype control antibody or 1D11 anti-TGF-β antibody (Left panel) or with vehicle or LY2109761 (Right panel). Bone metastases were monitored by BLI once weekly. Median values per group are shown. Treatment with 1D11 antibody reduced the burden of bone metastases by approximately 70-80% (p = 0.001) compared to treatment with either vehicle or isotype control antibody. Similarly, LY2109761 treatment inhibited bone metastases compared to vehicle controls by approximately 55% (p = 0.039). B. Faxitron analysis of fore-and hind limbs of tumor-bearing animals. Both 1D11 and LY2109761 treatment resulted in significant reductions in the total extent of SCP2TR-induced osteolytic bone lesions. Unpaired 2-sided t-test was used for comparisons. C. Treatment of bone-tropic SCP2TR inoculated mice with the 1D11 antibody was associated with prolongation of survival of the test animals (n = 10) compared to control animals (n = 12) (p = 0.06, Log-Rank test). D. Mice were inoculated with lung-tropic 4175TR cells via tailvein injection and treated with vehicle, 13C4 or 1D11 (Left panel) or with vehicle or LY2109761 (Right panel). Treatment with 1D11 antibody reduced the metastatic burden to lungs by approximately 25-40% (p = 0.001, Kruskall-Wallis test) compared to treatment with either vehicle or isotype control antibody. Similarly, LY2109761 treatment reduced the burden of lung metastases compared to vehicle by approximately 40% (p = 0.079). E. Treatment of mice inoculated with post dormancy bone tropic 2860TR cells with 1D11 antibody reduced the metastatic burden to bones by between 55-80% compared to treatment with vehicle or isotype control antibody (p = 0.019).