D. Zangani et al., Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells, EXP CELL RE, 247(2), 1999, pp. 399-409
Mammary epithelial organoids (MEO), isolated from pubescent rats, were cult
ured within a reconstituted basement membrane in transwell inserts, in the
presence or absence of mature mammary adipocytes in the lower well. This sy
stem allowed for free medium exchange between the two compartments, without
direct cell-to-cell contact. When cultured in serum-free medium supplement
ed with insulin, prolactin, hydrocortisone, progesterone, and various epide
rmal growth factor (EGF) concentrations, mammary adipocytes did not affect
epithelial cell growth, but enhanced epithelial differentiation. Casein and
lipid accumulations were monitored as indicators of functional differentia
tion of MEG. Mammary adipocytes significantly enhanced casein and lipid acc
umulation within the MEG, independently of EGF concentration. Furthermore,
adipocytes induced MEO to preferentially undergo alveolar morphogenesis, in
hibited squamous outgrowth, and increased lumen size. These findings demons
trate that morphological and functional differentiation of mammary epitheli
al cells is profoundly enhanced by the adipose stroma and that these effect
s are mediated by diffusible paracrine factors. This new model can be explo
ited in future studies to define the mechanisms whereby hormones and growth
factors regulate mammary gland development and carcinogenesis. Moreover, i
t could complement in vivo reconstitution/transplantation studies, which ar
e currently employed to evaluate the role of specific gene deletions in the
regulation of mammary development. (C) 1999 Academic Press.