Expression of integrin subunits in the human infant breast correlates with morphogenesis and differentiation

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Abstract
Integrins are widely expressed on normal tissues and their function is considered critical directly or indirectly with the control of cell growth and differentiation. Also, they are likely to play a crucial role in cell–matrix interactions during development. As the human breast develops after birth, it provides a rare opportunity in which to study human organogenesis. We have examined the distribution of integrins in the human infant breast with the aim of elucidating the possible role of these molecules in morphogenesis and differentiation. Necropsy breast specimens from six male and eight female infants, ranging in age from 1 day to 9 months, were used in this study. Cryostat sections were stained by the avidin-biotin complex technique, using a panel of monoclonal antibodies (MAbs) which recognize β1, α2, α6, β4, αv, and αvβ3 integrin chains, which are candidate molecules for a role in mammory morphogenesis. MAbs to β1 (DH12) and α2 (HAS3) showed positive membrane and cytoplasmic staining of basal cells and luminal epithelial cells. In addition, positive staining for the β1 integrin chain was found on fibroblasts. A MAb which recognizes the α6 chain (MP4F10) showed positive staining of the basal cells and heterogeneous staining of the luminal epithelial cells, whilst β4 chain (439-9B) showed positive staining in the basement membrane domain of the basal cells with no staining of the luminal epithelial cells. There was a positive correlation between the intensity of expression and the structural development of the ductal system, with integrin expression reduced or absent in the end buds and lateral buds. These data provide evidence that some integrin molecules are expressed in a pattern that correlates with the morphological and functional differentiation of the normal mammary gland. Changes in the expression and function of integrins may have an inductive role in the development of the normal mammary gland.