The contribution of adhesion signaling to lactogenesis

Abstract

The mammary gland undergoes hormonally controlled cycles of pubertal maturation, pregnancy, lactation, and involution, and these processes rely on complex signaling mechanisms, many of which are controlled by cell-cell and cell-matrix adhesion. The adhesion of epithelial cells to the extracellular matrix initiates signaling mechanisms that have an impact on cell proliferation, survival, and differentiation throughout lactation. The control of integrin expression on the mammary epithelial cells, the composition of the extracellular matrix and the presence of secreted matricellular proteins all contribute to essential adhesion signaling during lactogenesis. In vitro and in vivo studies, including the results from genetically engineered mice, have shed light on the regulation of these processes at the cell and tissue level and have led to increased understanding of the essential signaling components that are regulated in temporal and cell specific manner during lactogenesis. Recent studies suggest that a secreted matricellular protein, CTGF/CCN2, may play a role in lactogenic differentiation through binding to β1 integrin complexes, enhancing the production of extracellular matrix components and contributions to cell adhesion signaling.

Mid‐region parathyroid hormone‐related protein is a genome‐wide chromatin‐binding factor that promotes growth and differentiation of HB2 epithelial cells from the human breast

“…When HB2 cells were grown within collagen gels a down-regulation of ITGA2 in all the conditions tested, being under the detection limit of PCR, and an upregulation of ITGB1 in the presence of HGF and/or PTHrP supplements were found. Literature data indicate that β1-containing integrins are involved in alveologenesis and lactogenesis in vivo and in vitro [45]. By consequence, the obtained data are in line with the hypothesis that in the latter experimental conditions HB2 cells undergo a proliferation program addressed to the formation of mammary acini endowed with differentiated secretory function.…”

Molecular Aspects of Adipoepithelial Transdifferentiation in Mouse Mammary Gland

“…C, D, both right). It is known that intricate remodeling of the ECM is necessary for mammary alveologenesis and our data suggest that ECM components need to be downregulated for alveologenesis to take place. Furthermore, “cytoskeleton organization,” “vasculature development,” and “cell motility/locomotion” are found when mapping the downregulated genes, indicating that these essential pregnancy processes are continually downregulated during late pregnancy (>day 10).…”

Milk lipid composition is modified by perinatal exposure to bisphenol A

“…Taken together, the previous and present results suggest that perinatal exposure to low doses of BPA delays alveolar maturation during the secretory activation of the mammary gland. The interaction between epithelial cells and the extracellular matrix, especially the basement membrane, is critical for successful lactogenic differentiation (Morrison and Cutler, 2010). The exposure of the mammary gland to BPA during critical periods of morphogenesis could modify the mechanical properties of the extracellular matrix, resulting in a delay in alveolar maturation during secretory activation.…”