Laminin alpha 5 is Necessary for Mammary Epithelial Growth and Function by Maintaining Luminal Epithelial Cell Identity

Englund J.I., Cojoc H., Blaas L., Ritchie A., Pentinmikko N., Döhla J., Munne P., Patarroyo M., Klefström J., Ivaska J., Katajisto P.

Here, the authors demonstrate that the expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth and function. α5 chain laminin isoforms are mainly expressed by the luminal epithelial cells, and it is necessary for pubertal mammary gland growth, pregnancy-induced gland remodeling, and for alveolar function. Adhesion to α5 chain containing laminin promotes luminal traits in both luminal and basal epithelial cells and reduces progenitor activity of basal epithelial cells. Mechanistically, we show that loss of α5 chan laminins interferes with the differentiation of hormone receptor-positive luminal cells, which results in reduced Wnt4 expression and defective crosstalk between luminal and basal epithelial cells during gland remodeling. Our results reveal a novel BM-mediated mechanism, which regulates mammary gland remodeling and function via the specification of luminal epithelial cells.