A Novel 3-Dimensional Co-culture Method Reveals a Partial Mesenchymal to Epithelial Transition in Breast Cancer Cells Induced by Adipocytes
Cancer metastases are accountable for almost 90% of all human cancer related deaths including from breast cancer (BC). Adipocytes can alter the tumor microenvironment, which can promote metastasis by inducing an epithelial-to-mesenchymal transition (EMT) in BC cells. However, the role of adipocytes during the mesenchymal-to-epithelial transition (MET), that can be important in metastasis, is not clear. To understand the effect of adipocytes on the BC progression, there is a requirement for a better in vitro 3-dimensional (3D) co-culture system that mimics the breast tissue and allows for more accurate analysis of EMT and MET. We developed a co-culture system to analyze the relationship of BC cells grown in a 3D culture with adipocytes. We found that adipocytes and adipocyte-derived conditioned media, but not pre-adipocytes, caused the mesenchymal MDA-MB-231 and Hs578t cells to form significantly more epithelial-like structures when compared to the typical stellate colonies formed in control 3D cultures. SUM159 cells and MCF7 cells had a less dramatic shift as they normally have more epithelial-like structure in 3D culture. Biomarker expression analysis revealed that adipocytes only induced a partial MET with proliferation unaffected. In addition, adipocytes had reduced lipid droplet size when co-cultured with BC cells. Thus, we found that physical interaction with adipocytes and ECM changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumor formation.
Keywords3-dimensional culture Co-culture system ECM Adipocytes Triple negative breast cancer Mesenchymal to epithelial transition Metastasis
Funding provided to SLC by the Memorial University of Newfoundland (210525), a New Investigator Award from the Beatrice Hunter Cancer Research Institute (207939), and the Cancer Research Society (22130). An NSERC Discovery Grant to AVP provided funding for optimization of the 3D culture model (RGPIN-2017-3977). NKP was supported by a trainee award and a Skills Acquisition Program award from the Beatrice Hunter Cancer Research Institute with funds provided by The Terry Fox Strategic Health Research Training Program in Cancer Research at CIHR and by Memorial University of Newfoundland.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants or animals.
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