1. Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2. Department of Plastic Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
3. Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4. PhD. Programme in Translational Medicine, Kaohsiung Medical University, Kaohsiung, and Academia Sinica, Taipei, Taiwan
5. Center of Teaching and Research, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
6. Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
7. Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linko, Taoyuan, Taiwan
8. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
* These authors contributed equally to this work.
Background: The application of adipose tissue-derived stromal cells (ASCs) in regenerative medicine has become a growing trend due to its abundance and differentiation potentials. However, several breast cancer studies indicated that ASCs promote tumor progression, therefore, the use of ASCs for reconstruction after oncological surgery poses potential risks. In this study, we aimed to examine whether cancerous or non-cancerous breast cells will exhibit different responses to ASC-derived CM.
Methods: ASCs were isolated from residuals of subcutaneous adipose tissue obtained from patients undergoing surgery. Cancerous MCF-7, MDA-MB231, and MDA-MB468 cell lines and one non-cancerous M10/H184B5F5 cell line were cultured with variant concentrations of ASC-derived conditioned medium (CM) for analysis.
Results: ASC-derived CM significantly reduced cell viability by triggering apoptosis in MCF-7, MDA-MB231, and MDA-MB468 cell lines. ATM-Chk2-dependent DNA damage response was activated early in cancer cells when exposed to ASC-derived CM. By contrast, prompted cell proliferation instead of cell death was detected in M10/H184B5F5 cells under the treatment of lower CM concentration. Even when exposed to the highest concentration of CM, only cell cycle arrest accompanied by a weak DNA damage response were detected in M10/H184B5F5 cells, no cell deaths were observed.
Conclusions: Overall, this study demonstrated that cancerous and non-cancerous breast cells respond differently to ASC-derived CM. ASC-derived CM triggered significant cell death in breast cancer cell lines, however non-cancerous breast cells exhibited dissimilar response to ASC-derived CM.
Keywords: adipose tissue-derived stromal cell, ASCs, breast cancer cell line, apoptosis