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Vimentin plays a functional role in mammary gland regeneration

Reetta Virtakoivu, Emilia Peuhu, Anja Mai, Anni Wärri, Johanna Ivaska
doi: https://doi.org/10.1101/134544
Reetta Virtakoivu
1Centre for Biotechnology, University of Turku, 20520 Turku, Finland
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Emilia Peuhu
1Centre for Biotechnology, University of Turku, 20520 Turku, Finland
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Anja Mai
1Centre for Biotechnology, University of Turku, 20520 Turku, Finland
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Anni Wärri
1Centre for Biotechnology, University of Turku, 20520 Turku, Finland
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Johanna Ivaska
1Centre for Biotechnology, University of Turku, 20520 Turku, Finland
2Department of Biochemistry and Food Chemistry, University of Turku, 20520 Turku, Finland
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Abstract

In the mammary gland, vimentin intermediate filaments are expressed in stromal cells and in basal epithelial cell populations including gland-reconstituting mammary stem cells (MaSC), with largely undefined functions. Here, we studied how vimentin deficiency affects mouse mammary gland development. Our results demonstrate that in adult vimentin knockout mice (Vim-/-) mammary ductal outgrowth is delayed. The adult Vim-/- glands are characterised by dilated ducts, an imbalance in the proportion of basal to luminal mammary epithelial cells and a reduction in cells expressing Slug (Snai2), an established MaSC regulator. All of these features are indicative of reduced progenitor cell activity. Accordingly, isolated Vim-/- mammary epithelial cells display reduced capacity to form mammospheres, and altered organoid structure, compared to wt counterparts, when plated in a 3D matrix in vitro. Importantly, altered basal epithelial cell number translates into defects in Vim-/- mammary gland regeneration in vivo in cleared fat pad transplantation studies. Furthermore, we show that vimentin contributes to stem-like cell properties in triple negative MDA-MB-231 breast cancer cells, wherein vimentin depletion reduces tumorsphere formation and alters expression of breast cancer stem cell-associated surface markers. Together, our findings identify vimentin as a positive regulator of stemness in the developing mouse mammary gland and in breast cancer cells.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 05, 2017.
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Vimentin plays a functional role in mammary gland regeneration
Reetta Virtakoivu, Emilia Peuhu, Anja Mai, Anni Wärri, Johanna Ivaska
bioRxiv 134544; doi: https://doi.org/10.1101/134544
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Vimentin plays a functional role in mammary gland regeneration
Reetta Virtakoivu, Emilia Peuhu, Anja Mai, Anni Wärri, Johanna Ivaska
bioRxiv 134544; doi: https://doi.org/10.1101/134544

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