title: Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model.
abstract: The establishment of hormone target breast cells in the 1970's resulted in suitable models for the study of hormone control of cell proliferation and gene expression using two-dimensional (2D) cultures. However, to study mammogenesis and breast tumor development in vitro, cells must be able to organize in three-dimensional (3D) structures like in the tissue. We now report the development of a hormone-sensitive 3D culture model for the study of mammogenesis and neoplastic development. Hormone-sensitive T47D breast cancer cells respond to estradiol in a dose-dependent manner by forming complex epithelial structures. Treatment with the synthetic progestagen promegestone, in the presence of estradiol, results in flat epithelial structures that display cytoplasmic projections, a phenomenon reported to precede side-branching. Additionally, as in the mammary gland, treatment with prolactin in the presence of estradiol induces budding structures. These changes in epithelial organization are accompanied by collagen remodeling. Collagen is the major acellular component of the breast stroma and an important player in tumor development and progression. Quantitative analysis of second harmonic generation of collagen fibers revealed that collagen density was more variable surrounding budding and irregularly shaped structures when compared to more regular structures; suggesting that fiber organization in the former is more anisotropic than in the latter. In sum, this new 3D model recapitulates morphogenetic events modulated by mammogenic hormones in the breast, and is suitable for the evaluation of therapeutic agents.
authors.affiliation: 1 Cell, Molecular, and Developmental Biology Program, Department of Anatomy and Cellular Biology, Tufts University School of Medicine , Boston, Massachusetts.
authors.forename: Lucia
authors.initials: L
authors.lastname: Speroni
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Whitt
authors.forename: Joanna
authors.initials: J
authors.lastname: Xylas
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Quinn
authors.forename: Adeline
authors.initials: A
authors.lastname: Jondeau-Cabaton
authors.forename: Clifford
authors.initials: C
authors.lastname: Barnes
authors.forename: Irene
authors.initials: I
authors.lastname: Georgakoudi
authors.forename: Carlos
authors.initials: C
authors.lastname: Sonnenschein
authors.forename: Ana M
authors.initials: AM
authors.lastname: Soto
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000254:growth & development*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects / Q000254:growth & development*; D008954:Models, Biological; D011397:Promegestone / Q000494:pharmacology*; D051381:Rats; D011980:Receptors, Progesterone / Q000378:metabolism; D046509:Tissue Culture Techniques / Q000379:methods*
chemical_list: D000199:Actins; D015820:Cadherins; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone; D004958:Estradiol; D003094:Collagen; D011397:Promegestone