Institute for Frontier Materials, Deakin University, Geelong, 3216, Australia.
Division of Bioinformatics, Walter and Eliza Hall Medical Research Institute, 3000, Melbourne, Australia.
Cell Tissue Res. 2021 May;384(2):333-352. doi: 10.1007/s00441-020-03360-0. Epub 2021 Jan 13.
Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.
评估乳源激素在人类乳腺发育中的作用受到获取组织样本的限制，因此，开发具有与乳腺分泌性肺泡相似功能的体外三维乳腺球体模型可以帮助克服这一不足。在这项研究中，使用在鼠细胞外基质或琼脂糖上生长的人乳腺上皮细胞对乳腺球体模型进行了表征，结果表明胰岛素对于乳腺球体的形成是必需的。胰岛素被证明可以上调细胞外基质基因。对这些乳腺球体的微阵列分析显示，分化、细胞-细胞连接和细胞骨架组织功能上调，这表明乳腺球体的形成可能通过整合素信号通路进行调节。胰岛素和 IGF-1 对乳腺球体信号作用的比较表明，尽管 IGF-1 可以诱导形成球形结构，但细胞不能正确极化，因为极化基因没有上调，也不能诱导乳蛋白基因的表达。这项研究表明胰岛素在乳腺腺泡发育中的分泌分化和功能中起着重要作用，这表明肥胖和妊娠期糖尿病妇女的泌乳效率可能降低。
