Artikel
Adipose-derived mesenchymal stem cells may promote breast cancer growth and metastatic spread
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Veröffentlicht: | 3. September 2014 |
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Gliederung
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Stem-cell enriched fat grafting has recently been proposed for reconstructive purposes on the breast level. This novel approach however has raised concerns about safety of stem cell-based therapies, especially in the post-cancer scenario. The aim of the present study was to investigate the interactions between human adipose-derived mesenchymal stem cells (ASCs) and human breast cancer cells (MCF-7- and MDA cell line), while focusing on the tumor microenvironment, tumor growth and metastatic spread.
Human ASCs (CD34-CD73+CD90+CD105+) and MDA or MCF-7 breast cancer cell lines were used in this study. In vitro co-culture systems and assays were utilized for assessment of cytokine analysis and cell viability. An in-vivo breast cancer model in nu/nu mice was used for assessment of cancer progression and metastasis. Different proportional ratios of ASCs and MDA/MCF-7 cells were investigated. Tumor and metastatic tissue samples were analyzed with multiplex assays for oncogene expression, growth factors and metastatic phenotype markers. In vivo, metastatic spread (40% vs. 0% in controls) and mean tumor size (408±527mg vs. 38±99mg in controls, p<0.01) were both significantly increased in MDA tumor bearing animals receiving higher ASC aliquots. In vitro, these results were paralleled by up-regulation of RANTES, eotaxin and TNF-a expression. ASC treatment induced phenotypic switching in MCF-7 tumors, with coincident expression of HER2 oncogene, follistatin and osteopontin. In vivo tumor growth was significantly (p<0.05) promoted. Also metastatic spread was observed in 20% in comparison to 0% in cancer controls without ASC influence.
Our results suggest that human ASCs used in post mastectomy reconstruction or aesthetic breast augmentation may actually promote breast cancer. This may not necessarily preclude ASC use, but emphasizes due consideration of a dose dependent effect of such therapies and careful patient selection.