Targeting BMP-1 enhances anti-tumoral effects of doxorubicin in metastatic mammary cancer: common and distinct features of TGF-β inhibition. in Breast cancer research and treatment / Breast Cancer Res Treat. 2025 Jan 10. doi: 10.1007/s10549-024-07592-4.

2025

Tipo pubblicazione

Journal Article;

Autori/Collaboratori (4)Vedi tutti...

Yerlikaya A
Department of Medical Biology, Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey.
Riganti C
Department of Oncology, University of Torino, Via Nizza 44, 10126, Turin, Italy.
Haksever S
Department of Medical Pharmacology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.

et alii...

Abstract

PURPOSE: Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process. In addition, secretion of bone morphogenetic protein 1 (BMP-1), which is crucial for the proteolytic release of TGF-β, was markedly high in metastatic mammary cancer cells compared to non-metastatic cells. Although TGF-β inhibitors are in clinical trials, systemic inhibition of TGF-β may produce heavy side effects. We here hypothesize that inhibition of BMP-1 proteolytic activity inhibits TGF-β activity and induces anti-tumoral effects. METHOD AND RESULTS: Effects of specific BMP-1 inhibitor on liver and brain metastatic murine mammary cancer cells (4TLM and 4TBM), as well as on human mammary cancer MDA-MB-231 and MCF-7 cells, were examined and compared with the results of TGF-β inhibition. Inhibition of BMP-1 activity markedly suppressed proliferation of cancer cells and enhanced anti-tumoral effects of doxorubicin. Inhibition of BMP-1 activity but not of TGF-β activity decreased colony and spheroid formation. Differential effects of BMP-1 and TGF-β inhibitors on TGF-β secretion was also observed. CONCLUSIONS: These results demonstrated for the first time that the inhibition of BMP-1 activity has therapeutic potential for treatment of metastatic mammary cancer and enhances the anti-tumoral effects of doxorubicin.

PMID : 39792296

DOI : 10.1007/s10549-024-07592-4