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Breastfeeding is essential for a baby’s first few months and can even reduce a mother’s risk of breast cancer. The exact cause is unclear, but it could be due to the associated hormonal changes that delay the mother’s menstrual cycles. This delay reduces the mother’s lifetime exposure to menstrual cycle hormones like estrogen that can promote breast cancer cell growth.
As a mother produces milk in a process called lactation, the mammary gland’s tissues are structurally reorganized or renewed. This renewing ultimately produces a mature tree-like network of ducts that branch out from an epithelial bud. This very large ductal tree consists of an inner layer of luminal epithelial cells and a basal layer of myoepithelial cells. Luminal cells line the inside space of this tree and can produce secretory proteins. Meanwhile, myoepithelial cells surround and protect the luminal cells and have the ability to contract. The tree itself is embedded in a special tissue that contains various immune and mesenchymal cells.
These different cells in the mammary gland aid with the breastfeeding process. Luminal cells evolve into mature secretory cells that produce and secrete milk components during lactation. Meanwhile, myoepithelial cells help transport milk from the secretory cells to the nipple.
Learning more about the changes in the mammary gland’s tissues and cells can help us understand more about lactation and may even help explain exactly why breastfeeding lowers breast cancer risk. It is difficult to acquire tissue samples from lactating human mammary glands. But, as researchers from Cambridge, UK have seen for the first time, cells from breast milk can provide useful insight as well.
In their study, they isolated cells from non-lactating breast tissues and from human milk and analyzed them via single-cell RNA sequencing. In single-cell RNA sequencing, messenger RNA molecules, which encode genetic information for different proteins in the cell, are quantitatively assessed in individual cells. With this analysis, they were able to monitor changes in the expression of various genes in the human mammary gland and ultimately characterize the composition of non-lactating and lactating cells.
Their results revealed great heterogeneity in breast milk. Milk samples were found to have two epithelial cell clusters, each with distinct transcription factors. Both clusters expressed markers for secretory luminal cells, as well as genes important for milk proteins and milk fat secretion. In addition, some luminal cells were surprisingly found to express genes that help modulate the immune system. These comparisons between lactating and non-lactating cells provided insight into how epithelial cells differentiate as the mammary gland matures and what genes may be involved in the biosynthesis of milk components.
Lastly, epithelial cells in milk were found to resemble luminal progenitor (LP) cells, which are luminal cells with stem cell-like properties. LP cells are thought to give rise to basal-like breast cancers when mutations transpire. Furthermore, in a separate study, they found alterations in the expression of various secreted milk proteins in mouse LP cells when a tumor suppressor gene is perturbed and tumorigenesis starts to occur. Therefore, studying breast milk cells can give a glimpse into the mechanism behind this phenomenon and can potentially be useful in research on the early stages of breast cancer.
This study shows that breast milk cells, which were previously thought to be dead or dying cells, are actually alive. And by studying breast milk cells, which are relatively easy to collect, many details about mammary gland function during lactation can be revealed. The fact that the breast milk cells themselves can be studied opens up a whole window of opportunities for research, which can hopefully lead to a better understanding of early breast cancer development.
Edited by Mahrukh Fatima
Primary Work Cited:
Twigger, AJ., Engelbrecht, L.K., Bach, K. et al. Transcriptional changes in the mammary gland during lactation revealed by single-cell sequencing of cells from human milk. Nat Commun 13, 562 (2022). https://doi.org/10.1038/s41467-021-27895-0
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