The impact of human adipose tissue-derived stem cells on breast cancer cells: implications for cell-assisted lipotransfers in breast reconstruction

Abstract

BackgroundIn this study we evaluated the interactions of human adipose tissue-derived stem cells (ADSCs) and different human breast cancer cell lines (BRCAs) with regard to the safety of cell-assisted lipotransfers for breast reconstruction and a thereby unintended co-localization of ADSCs and BRCAs.MethodsADSCs were co-cultured with five different human BRCAs (MCF-7, MDA-MB-231, SK-BR-3, ZR-75-30, and EVSA-T) and primary BRCAs from one patient in a transwell system, and cell-cell-interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real-time polymerase chain reaction (PCR) of more than 300 tumor-associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPs). Results of co-culture were compared to those of the respective monoculture.ResultsQuantitative real-time PCR revealed remarkable changes in the expression of multiple tumor-associated genes in co-culture compared to monocultures of both ADSCs and BRCAs. Concomitantly, the concentration of several tumor-associated proteins, such as cytokines and MMPs, were strongly increased in co-culture. Furthermore, exclusively in co-culture with ADSCs, the different BRCAs were exposed to several important tumor-modulating proteins, such as CCL2, HGF, or interleukins.Co-culture did not significantly affect cellular proliferation of either ADSCs or BRCAs (p > 0.05). The migration of MCF-7 and MDA-MB-231 BRCAs was significantly increased in co-culture with ADSCs by a mean of 11% and 23%, respectively (p = 0.04 and 0.012), as well as that of ADSCs in co-culture with MDA-MB-231, ZR-75-30, and EVSA-T (+11–15%, p = 0.035–0.045). Co-culture with MDA-MB-231, SK-BR-3, and EVSA-T BRCAs significantly increased the invasive behavior of ADSCs by a mean of 24–41% (p = 0.014–0.039). There were no significant differences in the in vitro invasive properties of BRCAs in co-culture compared to monoculture. An in vitro angiogenesis assay revealed an increased tube formation of conditioned media from co-cultured BRCAs and ADSCs compared to the respective monocultures.ConclusionThis study further elucidates the possible interactions of primary human ADSCs with human BRCAs, pointing towards a potential increased oncological risk which should not be neglected when considering a clinical use of cell-assisted lipoaspirates in breast reconstruction.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0579-1) contains supplementary material, which is available to authorized users.

The Role of MMP8 in Cancer: A Systematic Review

“…MMP8 mRNA expression is only detected in MDA-MB-231 cells [121,123,124], except in one study that found no expression [125]. Co-culture with adipose tissue-derived mesenchymal stem cells, a driver of tumorigenesis, did not affect the MMP8 expression of breast cancer cells [126]. Although MMP8 was mainly found to be expressed by metastatic cell lines and not the non-metastatic MCF-7 cell line, many [123,124,127] have shown that MMP8-expressing breast cancer cell lines are less invasive in vitro and generate less metastases in mice in vivo.…”

Obesity-Altered Adipose Stem Cells Promote ER+ Breast Cancer Metastasis through Estrogen Independent Pathways

“…Studies have demonstrated that ASCs promote breast cancer cell migration, stemness and promote angiogenesis [30,31,32]. ObASCs have been shown to promote tumor growth and metastasis of MCF7 through increased secretion of leptin, which upregulates aromatase and ERα [24].…”

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

“…Specific regenerative properties of ASCs could be used in breast reconstructive surgery after a mastectomy has been performed. However, its utility in this condition is quite controversial and could raise concerns about their proliferative effect on residual tumor cells [139,140]. Direct myocardial injection of allogeneic ASCs has been found to be safe and has presented a tendency toward improvement in cardiac function in patients with ischemic heart disease and ischemic heart failure [141].…”