S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.

Jo, S. H.; Heo, W. H.; Hong, B. S.; Kim, J. H.; Lee, J.; Lee, E.-S.; Lee, H.-B.; Han, W.; Park, Y.; Lee, D.-S.; Kwon, N. H.; Park, M. C.; Chae, J.; Kim, J.-I.; Noh, D.-Y.; Moon, H.-G.

doi:10.1101/312884

bioRxiv · 10.1101/312884

S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.

Jo, S. H.·Heo, W. H.·Hong, B. S.·Kim, J. H.·Lee, J.·Lee, E.-S.·Lee, H.-B.·Han, W.·Park, Y.·Lee, D.-S.·Kwon, N. H.·Park, M. C.·Chae, J.·Kim, J.-I.·Noh, D.-Y.·Moon, H.-G.

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Abstract

To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell-cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell-cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.

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Jo, S. H., Heo, W. H., Hong, B. S., Kim, J. H., Lee, J., Lee, E.-S., Lee, H.-B., Han, W., Park, Y., Lee, D.-S., Kwon, N. H., Park, M. C., Chae, J., Kim, J.-I., Noh, D.-Y., Moon, H.-G.. 2018-05-04. S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.. https://doi.org/10.1101/312884

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