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Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial cells and promotes invasive growth

Published in Biochemical and Biophysical Research Communications. 2007, vol. 353, no. 3, p. 817-22
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.
Keywords AnimalsAnthracenes/pharmacologyBone Morphogenetic Protein 4Bone Morphogenetic Proteins/pharmacologyButadienes/pharmacologyCell Transformation, Neoplastic/pathologyCells, CulturedEpithelial Cells/drug effects/pathologyFemaleHumansImidazoles/pharmacologyMammary Glands, Animal/cytologyMiceMitogen-Activated Protein Kinases/antagonists & inhibitorsNeoplasm Invasiveness/physiopathologyNitriles/pharmacology
PMID: 17189614
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MONTESANO, Roberto. Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial cells and promotes invasive growth. In: Biochemical and Biophysical Research Communications, 2007, vol. 353, n° 3, p. 817-22. https://archive-ouverte.unige.ch/unige:3873

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Deposited on : 2009-10-22

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