Epithelial vimentin plays a functional role in mammary gland development

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, with largely undefined functions. Here, we have studied how vimentin deficiency affects mouse mammary gland development. We find that, in adult vimentin knockout mice (<i>Vim^-/-</i> ), mammary ductal outgrowth is delayed. The adult <i>Vim^-/-</i> glands display dilated ducts and a reduced basal-to-luminal mouse mammary epithelial cell (MMEC) ratio indicative of altered progenitor cell activity. Accordingly, isolated <i>Vim^-/-</i> MMECs form fewer mammospheres and basal-like organoids <i>in vitro</i> than their wild-type counterparts. Importantly, reduced basal MMEC number translates into defects in <i>Vim^-/-</i> mammary gland regeneration <i>in vivo</i> Global gene expression profiling of basal MMECs reveals that lack of vimentin alters multiple pathways, including adhesion, cancer and Wnt signalling. Furthermore, vimentin contributes to stem-like cell properties in MDA-MB-231 breast cancer cells, wherein vimentin depletion reduces tumoursphere formation and attenuates 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.