Peuhu Emilia, Virtakoivu Reetta, Mai Anja, Wärri Anni, Ivaska Johanna
Centre for Biotechnology, University of Turku, 20520 Turku, Finland
Centre for Biotechnology, University of Turku, 20520 Turku, Finland.
Development. 2017 Nov 15;144(22):4103-4113. doi: 10.1242/dev.154229. Epub 2017 Sep 25.
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 ( ), mammary ductal outgrowth is delayed. The adult glands display dilated ducts and a reduced basal-to-luminal mouse mammary epithelial cell (MMEC) ratio indicative of altered progenitor cell activity. Accordingly, isolated MMECs form fewer mammospheres and basal-like organoids than their wild-type counterparts. Importantly, reduced basal MMEC number translates into defects in mammary gland regeneration 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.
在乳腺中，波形蛋白中间丝在基质细胞和基底上皮细胞群体中表达，包括参与腺体重建的乳腺干细胞，其功能大多尚不明确。在此，我们研究了波形蛋白缺乏如何影响小鼠乳腺发育。我们发现，在成年波形蛋白基因敲除小鼠中，乳腺导管的生长延迟。成年小鼠的腺体显示出扩张的导管，且基底上皮细胞与管腔上皮细胞的比例降低，这表明祖细胞活性发生了改变。相应地，与野生型对应细胞相比，分离得到的乳腺上皮细胞形成的乳腺球和基底样类器官更少。重要的是，基底乳腺上皮细胞数量的减少导致乳腺再生出现缺陷。对基底乳腺上皮细胞进行全基因表达谱分析发现，波形蛋白的缺失改变了包括黏附、癌症和Wnt信号传导在内的多种信号通路。此外，波形蛋白有助于MDA-MB-231乳腺癌细胞具有干细胞样特性，其中波形蛋白的缺失会减少肿瘤球的形成，并减弱乳腺癌干细胞相关表面标志物的表达。总之，我们的研究结果表明波形蛋白是发育中的小鼠乳腺和乳腺癌细胞干性的正向调节因子。
