The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction

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 prim...

Full description

Bibliographic Details
Main Authors: Asim Ejaz, Katherine S. Yang, Kaushik P. Venkatesh, Somaiah Chinnapaka, Lauren E. Kokai, J. Peter Rubin
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/23/9171
_version_ 1797546036160364544
author Asim Ejaz
Katherine S. Yang
Kaushik P. Venkatesh
Somaiah Chinnapaka
Lauren E. Kokai
J. Peter Rubin
author_facet Asim Ejaz
Katherine S. Yang
Kaushik P. Venkatesh
Somaiah Chinnapaka
Lauren E. Kokai
J. Peter Rubin
author_sort Asim Ejaz
collection DOAJ
description 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.
first_indexed 2024-03-10T14:24:23Z
format Article
id doaj.art-8392b80e0da1428b88f80db186b30833
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T14:24:23Z
publishDate 2020-12-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-8392b80e0da1428b88f80db186b308332023-11-20T23:08:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123917110.3390/ijms21239171The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast ReconstructionAsim Ejaz0Katherine S. Yang1Kaushik P. Venkatesh2Somaiah Chinnapaka3Lauren E. Kokai4J. Peter Rubin5Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USABackground: 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.https://www.mdpi.com/1422-0067/21/23/9171adipose-derived stem cellslipoaspiratesbreast cancer cellscell cycle and proliferation
spellingShingle Asim Ejaz
Katherine S. Yang
Kaushik P. Venkatesh
Somaiah Chinnapaka
Lauren E. Kokai
J. Peter Rubin
The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
International Journal of Molecular Sciences
adipose-derived stem cells
lipoaspirates
breast cancer cells
cell cycle and proliferation
title The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
title_full The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
title_fullStr The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
title_full_unstemmed The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
title_short The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction
title_sort impact of human lipoaspirate and adipose tissue derived stem cells contact culture on breast cancer cells implications in breast reconstruction
topic adipose-derived stem cells
lipoaspirates
breast cancer cells
cell cycle and proliferation
url https://www.mdpi.com/1422-0067/21/23/9171
work_keys_str_mv AT asimejaz theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT katherinesyang theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT kaushikpvenkatesh theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT somaiahchinnapaka theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT laurenekokai theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT jpeterrubin theimpactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT asimejaz impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT katherinesyang impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT kaushikpvenkatesh impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT somaiahchinnapaka impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT laurenekokai impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction
AT jpeterrubin impactofhumanlipoaspirateandadiposetissuederivedstemcellscontactcultureonbreastcancercellsimplicationsinbreastreconstruction