title: Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial cells and promotes invasive growth.
abstract: Bone morphogenetic proteins (BMPs) are multifunctional cytokines that regulate key developmental processes, but are also overexpressed in many carcinomas. To assess whether BMPs would influence the three-dimensional architecture of epithelial structures, we took advantage of an in vitro model in which mammary epithelial cells form alveolar-like spherical cysts in collagen gels. We found that BMP-4 has a dramatic, biphasic effect on the organization of epithelial cysts. When added in the concentration range of 1-10 ng/ml, the cytokine abrogates lumen formation and induces the outgrowth of multiple invasive cord-like structures. At higher concentrations (20-100 ng/ml), BMP-4 additionally disrupts cell-cell adhesion, resulting in cyst disintegration and scattering of individual cells into the surrounding collagen matrix. The finding that BMP-4 subverts the ability of mammary epithelial cells to form polarized lumen-containing structures and endows them with invasive properties supports the involvement of this cytokine in the progression of breast cancer.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland. Roberto.Montesano@medecine.unige.ch
authors.forename: Roberto
authors.initials: R
authors.lastname: Montesano
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009570:Nitriles / Q000494:pharmacology
chemical_list: D000873:Anthracenes; C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002070:Butadienes; D007093:Imidazoles; D009570:Nitriles; C113580:U 0126; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole