Adipose-Derived Stem Cells After Paclitaxel Treatment Demonstrate Decreased Function And Suppression Of Breast Cancer Cell Viability

Background: Following neoadjuvant or adjuvant chemotherapy for breast cancer resections, poor soft tissue wound healing can pose a major clinical challenge. Adipose-derived stem cells (ASCs) in clinically applied stromal vascular fractions are considered to play a positive role in wound healing (SVF) as evidenced by their increasing use in breast reconstructive procedures. Our study evaluated the potential confounding effects of Paclitaxel (PTX) on ASC proliferation and differentiation capacities and if PTX treated ASCs may subsequently influence tumor cell viability. Methods: IRB-approved human ASCs were isolated and treated with PTX at different concentrations. Proliferation, cell viability, and cell migration rates were measured by growth curves, MTT assays and scratch assays. ASCs were cultured in derivative-specific differentiation media with or without PTX (1uM) for 3 weeks. Adipogenic, osteogenic and endothelial differentiation levels were measured by quantitative RT-PCR, Oil-Red-O, Alizarin Red staining and cord formation on Matrigel, respectively. MDA-MB-231 (breast cancer cell line) and ASCs were co-cultured at equal cell numbers. ASC conditional media were collected every 3 days from ASC no-PTX treatment and PTX treated - washout groups. Results: PTX decreased proliferation of ASCs in a dose- and time-dependent manner. PTX treatment down-regulated the capacity of ASCs for adipogenic, osteogenic and endothelial differentiation (p Conclusion: Our results indicate that: 1) PTX inhibited ASC proliferation and decreased the multipotency differentiating capacity; and 2) Direct contact or treatment with conditional media from PTX treated ASCs suppressed tumor cell growth. In evaluating autologous ASCs for reconstructive procedures, this study may provide insight into poor soft tissue wound healing immediately following the removal of chemotherapy as well as decreased recurrence in breast cancer patients. Citation Format: William M. Harris, Michael Plastini, Telisha Ortiz, Nikolas Kappy, Jefferson Benites, Shaohua Chang, A. Lelani Fahey, Martha S. Matthews, Alexandre Hageboutros, Jeffrey P. Carpenter, Spencer Brown, Ping Zhang. Adipose-derived stem cells after Paclitaxel treatment demonstrate decreased function and suppression of breast cancer cell viability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4077. doi:10.1158/1538-7445.AM2015-4077