PMID- 33271950 OWN - NLM STAT- MEDLINE DCOM- 20210309 LR - 20210415 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 23 DP - 2020 Dec 1 TI - The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction. LID - 10.3390/ijms21239171 [doi] LID - 9171 AB - BACKGROUND: Autologous fat transfer in the form of lipoaspirates for the reconstruction of the breast after breast cancer surgery is a commonly used procedure in plastic surgery. However, concerns regarding the oncologic risk of nutrient-rich fat tissue are widely debated. Previous studies have primarily focused on studying the interaction between adipose-derived stem cells (ASCs) and breast cancer cells. METHODS: In this study, we performed a comprehensive analysis of the paracrine- and contact-based interactions between lipoaspirates, ASCs and breast cancer cell lines. An inverted flask culture method was used to study the contact-based interaction between lipoaspirates and breast cancer cells, while GFP-expressing breast cancer cell lines were generated to study the cell-cell contact interaction with ASCs. Three different human breast cancer cell lines, MCF-7, MDA-MB-231 and BT-474, were studied. We analyzed the impact of these interactions on the proliferation, cell cycle and epithelial-to-mesenchymal (EMT) transition of the breast cancer cells. RESULTS: Our results revealed that both lipoaspirates and ASCs do not increase the proliferation rate of the breast cancer cells either through paracrine- or contact-dependent interactions. We observed that lipoaspirates selectively inhibit the proliferation of MCF-7 cells in contact co-culture, driven by the retinoblastoma (Rb) protein activity mediating cell cycle arrest. Additionally, ASCs inhibited MDA-MB-231 breast cancer cell proliferation in cell-cell contact-dependent interactions. Quantitative real-time PCR revealed no significant increase in the EMT-related genes in breast cancer cells upon co-culture with ASCs. CONCLUSION: In conclusion, this study provides evidence of the non-oncogenic character of lipoaspirates and supports the safety of clinical fat grafting in breast reconstruction after oncological surgical procedures. In vivo studies in appropriate animal models and long-term post-operative clinical data from patients are essential to reach the final safety recommendations. FAU - Ejaz, Asim AU - Ejaz A AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. FAU - Yang, Katherine S AU - Yang KS AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. FAU - Venkatesh, Kaushik P AU - Venkatesh KP AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. FAU - Chinnapaka, Somaiah AU - Chinnapaka S AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. FAU - Kokai, Lauren E AU - Kokai LE AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. FAU - Rubin, J Peter AU - Rubin JP AD - Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA. LA - eng GR - R01 CA114246/CA/NCI NIH HHS/United States GR - R01-CA114246-08A1/NH/NIH HHS/United States PT - Journal Article DEP - 20201201 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (Culture Media, Conditioned) SB - IM MH - Adipose Tissue/*cytology MH - Biomarkers MH - Breast Neoplasms/*metabolism/pathology MH - *Cell Communication MH - Cell Differentiation MH - Cell Proliferation MH - Coculture Techniques MH - Culture Media, Conditioned MH - Female MH - Humans MH - Immunophenotyping MH - Lipectomy MH - Mammaplasty MH - Primary Cell Culture MH - Stem Cells/*metabolism PMC - PMC7731376 OTO - NOTNLM OT - adipose-derived stem cells OT - breast cancer cells OT - cell cycle and proliferation OT - lipoaspirates COIS- The authors indicated no potential conflict of interest. EDAT- 2020/12/05 06:00 MHDA- 2021/03/10 06:00 PMCR- 2020/12/01 CRDT- 2020/12/04 01:01 PHST- 2020/08/27 00:00 [received] PHST- 2020/11/19 00:00 [revised] PHST- 2020/11/27 00:00 [accepted] PHST- 2020/12/04 01:01 [entrez] PHST- 2020/12/05 06:00 [pubmed] PHST- 2021/03/10 06:00 [medline] PHST- 2020/12/01 00:00 [pmc-release] AID - ijms21239171 [pii] AID - ijms-21-09171 [pii] AID - 10.3390/ijms21239171 [doi] PST - epublish SO - Int J Mol Sci. 2020 Dec 1;21(23):9171. doi: 10.3390/ijms21239171.