Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice
21.01.2010
Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Müller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J, Peters C, Reinheckel T.
Proc Natl Acad Sci U S A 107(6):2497-502
In the MMTV-PyMT breast cancer mouse model we demonstrate that single deficiencies of the cysteine cathepsins B and Z have relatively minor effects on most parameters of breast cancer development in this model, but that combined deficiency of Ctsb and Ctsz results in a significantly reduced tumor and metastatic burden of PymT induced breast cancer in mice. Our data on reciprocal functional compensation both proteases in tumor promotion and the efficacy of their combined knockout suggest a combinational therapeutic strategy.
