Enhanced cancerous properties of breast cancer cell and brown adipocyte co-cultures compared to their fused cells (Poster Presentation)

Abstract

<p><strong>Background:</strong> The unique microenvironment of breast cancer (BC) surrounded by adipose tissue plays a critical role in tumorigenesis and metastasis. However, the underlying mechanisms of BC progression driven by various types of adipocytes are not fully elucidated. This study aims to understand the role of BC-adipocyte interaction in cancer invasiveness at cellular and molecular levels.</p><p><strong>Material and Methods:</strong> Preadipocytes (3T3L1 cell line)-derived mature adipocyte-like adipocytes (AL), brown adipocytes (BAT), white adipocytes (WAT) as well as adipose-derived stem cell (ASC) were labeled with red fluorescence cell tracker and were co-cultivated with green cell tracker-tagged hormone receptor-positive breast cancer cell (MCF7) respectively. The alteration of cells at morphological, genomic and numerical levels at serial time points were examined by time-lapsed confocal laser scanning microscopy, DNA fluorescence in situ hybridization (FISH), and flow cytometry. The invasiveness of cancer cells was investigated in terms of their proliferation, migration, and invasiveness. Furthermore, the functional role of adipocytes on BC was explored in a xenograft tumor mouse model. In addition, the underlying mechanism was explored regarding the role of mitochondrial function and relevant molecular signaling.</p><p><strong>Results:</strong> MCF7 co-cultured with all types of adipocytes showed a higher tumor activity than MCF7-BAT co-cultivation was the highest (4-fold increase in MTT and migration assay, p < 0.0001). Furthermore, the tumorigenic potential of the co-cultivated cells was also observed in the xenograft tumor mouse model, in which the in vivo tumor growth of co-cultivated cells was significantly higher than that of the MCF7 alone. Morphologically, MCF7-adipocyte cell-cell fusion was observed in all types of co-cultivation, and the fused cell proportion was significantly higher in MCF7-BAT than in other co-cultivation. Mechanistically, the transcriptional levels of empirical cell fusion and adipogenic metabolism molecules were substantially higher in co-cultivated cells. In addition, the cancer cells co-cultured with BAT showed higher intracellular mitochondrial content and were positively associated with more aggressive cancerous behavior. However, fused MCF7-BAT cells per se did not show superior invasiveness compared with other fused cells and the whole co-cultivation systems.</p><p><strong>Conclusion:</strong> Various adipocytes can spontaneously fuse with breast cancer cells without special induction or stimulation. Both co-cultures and fusion hybrid cells consistently displayed an obvious change towards a more malignant phenotype. Brown adipocyte has the strongest effect of promoting breast cancer invasiveness by increasing the mitochondrial content of the cancer cells independent of cell fusion.</p>