biostudies-literatureMatjan Stefin PThe Slovenian Research and Innovation Agency360https://www.ebi.ac.uk/biostudies/studies/S-EPMC12939340biostudies-literatureUnknown15(4)<b>Background/Objectives</b>: Cysteine cathepsins and their endogenous inhibitors have been shown to possess context-dependent functions in cancer progression, including the regulation of tumor metabolic pathways. Stefin B and cystatin C, intracellular and extracellular protease inhibitors, respectively, can modulate tumor biology through protease-dependent and protease-independent mechanisms. This study investigated their combined functions and potential roles as tumor promoters in breast cancer in a spontaneous breast cancer mouse model (PyMT mice). <b>Methods</b>: We generated PyMT transgenic mice lacking both stefin B and cystatin C (double-knockout, DKO) and compared their tumor growth kinetics, proliferation, apoptosis, and metastatic burden with those of wild-type control mice. ImmuCellsStefin B and Cystatin C Deficiency Suppresses Tumor Growth and Alters Tumor Microenvironment in a Breast Cancer Model.PMC12939340P1-0140Turk BMikhaylov GMatjan Stefin PZavrsnik JVasiljeva OButinar MfalseStefin B and Cystatin C Deficiency Suppresses Tumor Growth and Alters Tumor Microenvironment in a Breast Cancer Model.<b>Background/Objectives</b>: Cysteine cathepsins and their endogenous inhibitors have been shown to possess context-dependent functions in cancer progression, including the regulation of tumor metabolic pathways. Stefin B and cystatin C, intracellular and extracellular protease inhibitors, respectively, can modulate tumor biology through protease-dependent and protease-independent mechanisms. This study investigated their combined functions and potential roles as tumor promoters in breast cancer in a spontaneous breast cancer mouse model (PyMT mice). <b>Methods</b>: We generated PyMT transgenic mice lacking both stefin B and cystatin C (double-knockout, DKO) and compared their tumor growth kinetics, proliferation, apoptosis, and metastatic burden with those of wild-type control mice. Immu2026-01-01T00:00:00Z2026 Feb2026-07-11T03:19:07.373Z2026-07-11T03:09:48.53ZS-EPMC129393404174480310.3390/cells15040360