Myoepithelial cell diffeentiation in the developing mammary gland: Progressive acquisition of smooth muscle phenotype

Abstract

The most important portion of the mammary gland development occurs postnatally, with distinct periods of intensive morphogenesis taking place btween birth and puberty and during pregnancy and lactation. To characterize the differentiation process of mammary myopithlial cells, we have studied the expression patterns of several smooth musle phenotypic markers, including contractile proteins, α-smooth muscle-actin (α-SM-actin), smooth muscle myosin heavy chains (SM-MHC), and calponin; components of cell-extracellular matrix aderens junctions, phosphoglucomutase-related protein (PGM), vinculin variants, integrin subunits; and laminin variant chains in the developing rat mammary gland using immunofluorescence microscopy. α-SM-actin- and SM-MHC-positive cells were found first in newborn animals, while calponin, PGM, and α₁ integrin subunit began to be expressd in prepubertal animals (1.5 weeks). Vinculin, β₁ and α₃ integrin subunit were largely confined to the basal cell layer at all developmental stages examined with greater staining starting at 1.5 weeks. Meta-vinculin was identifed only in myoepithelial cells of the lactating gland. γ1 laminin chain was present in the mammary gland basement membrane throughout development, while the β2 chain was revealed in 3-week-old animals and accumulated later in pospubertal animals (7 weeks). Similarly, β2 laminin chain was absent from the forming alveoli basement membrane in pregnant rats and started to accumulate in the lactating gland. In addition to temporal changes, we have observed spatial differences in the distribution of the phenotypic markers. Both in pre- and in postpubertal animals, α-SM-actinand SM-MHC-positive cells of the growing ductal ends contained low amounts if any of calponin, PGM, and β2 laminin chain. We conclude that during postnatal development, mammary myoepithelial cells progressively acquire a differentiated phenotype as revealed by the expression of various smooth muscle markers. Maturation of the myoepithelial cells is accompanied by upregulation of the smooth muscle integrin expression followed by accumulation of β2-containing laminin variant. Thus, changes in adhesion system parallel with the myoepithelial cell differentiation.