Scientists at the University of Helsinki have discovered an essential factor in the extracellular matrix that regulates the functionality of breast tissue, for example during pregnancy.
The extracellular matrix (ECM) has already been recognized as an important building block for the growth of various epithelial cells, but rather as a scaffold. A new study shows that ECM can also regulate the function of epithelial cells.
Our tissues are made up of differentiated cell types, which perform specific, tightly controlled tasks. Normal tissue growth and function is only possible when the various differentiated cell types interact appropriately. The differentiation and function of the mammary epithelium are guided by a group of cells sensitive to the hormones estrogen and progesterone. In a recent study, it was discovered that these cells produce an ECM protein in their environment and that it regulates the growth and differentiation of the epithelium outside the cells. In particular, the production of this protein, Lama5, has been shown to enhance the functionality of these cells.
Hormone-sensitive cells can sense growth signals, such as signals from hormones and growth factors, and relay them to neighboring cells. When the Lama5 gene was deleted from these cells, they became unable to relay these signals and stopped the growth of the entire epithelium.
“This study shows that the extracellular environment produced by the cells themselves is an important factor for the identity and function of epithelial cells, and therefore for the whole tissue,” says assistant professor Pekka Katajisto of the University of Helsinki. The study was conducted in his lab.
Development during pregnancy and milk production is impaired
Hormone-sensitive cells were previously not known to participate in the generation of the surrounding ECM or even to have contact with the ECM.
“We observed that, surprisingly, hormone-sensing cells produced Lama5, which is essential for these cells to function properly. Without expression of the Lama5 gene, hormone-sensing cells will lose their identity and will not be able to support the growth of the epithelium during pregnancy, for example, ”explains Dr. Johanna Englund, lead author of the study.
The study was carried out using, for example, an organoid culture of epithelial cells isolated from mouse mammary glands. Organoids can under specific conditions be induced to produce milk.
“Our results suggest that the lack of ECM Lama5 factor also impairs milk production,” explains Englund.
The results of this study may help to understand how breast cancer is initiated. 70-80% of breast cancers come from hormone-detecting cells, and it is conceivable that these cancer cells also depend on Lama5 for their growth.
The study was carried out in the laboratory of assistant professor Pekka Katajisto, at HiLIFE and at the Institute of Biotechnology at the University of Helsinki.
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