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.

Keywords: Adhesion; CCN2; CTGF; Connective tissue growth factor; Integrin; Lactogenesis; Mammary gland; Signal transduction.

Fig. 1

Cell adhesion regulates essential pathways in lactogenesis. The binding of lactogens in conjunction with signals from integrin engagement initiate the critical changes that take place during lactogenic differentiation. The diagram includes the central pathways known to contribute to the initiation and control of lactogenesis. Dotted lines (.......) indicate pathways with multiple or incompletely known enzymatic steps

Fig. 2

The contribution of CTGF/CCN2 to lactogenic differentiation. The diagram includes the pathways known to be affected by CTGF/CCN2 during lactogenic differentiation of mammary epithelial cells in primary cells or established cell lines