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Observed Changes in the Morphology and Phenotype of Breast Cancer Cells in Direct Co-Culture with Adipose-Derived Stem Cells

Kuhbier, Joern W. M.D.; Bucan, Vesna Ph.D.; Reimers, Kerstin Ph.D.; Strauss, Sarah Ph.D.; Lazaridis, Andrea; Jahn, Sabrina; Radtke, Christine M.D.; Vogt, Peter M. M.D.

Plastic and Reconstructive Surgery: September 2014 - Volume 134 - Issue 3 - p 414–423
doi: 10.1097/PRS.0000000000000525
Breast: Special Topic

Background: Regarding aesthetics and long-term stability, cell-assisted lipotransfer is a promising method for breast reconstruction. Here, autologous fat grafts enriched with autologous adipose-derived stem cells are transferred. However, as adipose-derived stem cells secrete high amounts of growth factors, potential risks of tumor reactivation remain. In this study, influences of adipose-derived stem cells on inflammatory breast cancer cells were evaluated in a direct co-culture system.

Methods: Human adipose-derived stem cells were isolated and cultivated either alone or in a direct co-culture with the inflammatory breast carcinoma cell line T47D. At different time points, cell morphology was observed by scanning electron microscopy, cell membranes were stained by immunofluorescence, and gene expression was analyzed by real-time polymerase chain reaction.

Results: In co-cultures, T47D breast carcinoma cells showed tumorsphere-typical growth surrounded by a monolayer of adipose-derived stem cells. Direct cell-to-cell contacts could be observed between the two different cell types. Immunofluorescence revealed vesicular exchange and fusion between carcinoma cells and adipose-derived stem cells. Expression levels of transcriptional genes for typical malignancy markers were substantially higher in co-cultures compared with single cultures.

Conclusions: Direct intercellular contact between carcinoma cells and adipose-derived stem cells by means of exosomal vesicular exchange was revealed. Breast cancer cells displayed a change towards a more malignant phenotype associated with higher rates of metastasis and worsened prognosis. As cell-assisted lipotransfer is often performed after breast cancer surgery, transfer of adipose-derived stem cells might lead to deterioration of prognosis in case of recurrence as it has been described for inflammatory breast cancer.

Hannover, Germany

From the Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover.

Received for publication November 5, 2013; accepted May 28, 2014.

The first two authors contributed equally to this study.

Presented in part at the 17th Surgical Research Days, in Frankfurt, Germany, October 4 through 5, 2013; the Second Congress of the International Society of Plastic Regenerative Surgery, in Berlin, Germany, June 7 through 9, 2013; the 130th Congress of the German Society of Surgery, in Munich, Germany, April 30 through May 3, 2013; and the Seventh Fraunhofer Life Science Symposium, in Leipzig, Germany, November 29 through 30, 2012.

Disclosure: None of the authors has a financial interest in any of the products or devices mentioned in this article. This study received no external funding.

Joern W. Kuhbier, M.D., Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany,

©2014American Society of Plastic Surgeons