title: Microenvironment promotes tumor cell reprogramming in human breast cancer cell lines.
abstract: The microenvironment drives mammary gland development and function, and may influence significantly both malignant behavior and cell growth of mammary cancer cells. By restoring context, and forcing cells to properly interpret native signals from the microenvironment, the cancer cell aberrant behavior can be quelled, and organization re-established. In order to restore functional and morphological differentiation, human mammary MCF-7 and MDA-MB-231 cancer cells were allowed to grow in a culture medium filled with a 10% of the albumen (EW, Egg White) from unfertilized chicken egg. That unique microenvironment behaves akin a 3D culture and induces MCF-7 cells to produce acini and branching duct-like structures, distinctive of mammary gland differentiation. EW-treated MDA-MB-231 cells developed buds of acini and duct-like structures. Both MCF-7 and MDA-MB-231 cells produced β-casein, a key milk component. Furthermore, E-cadherin expression was reactivated in MDA-MB-231 cells, as a consequence of the increased cdh1 expression; meanwhile β-catenin - a key cytoskeleton component - was displaced behind the inner cell membrane. Such modification hinders the epithelial-mesenchymal transition in MDA-MB-231 cells. This differentiating pathway is supported by the contemporary down-regulation of canonical pluripotency markers (Klf4, Nanog). Given that egg-conditioned medium behaves as a 3D-medium, it is likely that cancer phenotype reversion could be ascribed to the changed interactions between cells and their microenvironment.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy ; Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: D'Anselmi
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Masiello
authors.affiliation: Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Proietti
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.affiliation: Department of Basic and Applied Medical Sciences, University "G. D'Annunzio", Chieti-Pescara, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pasqualato
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dobrowolny
authors.affiliation: Department of Anatomy, Histology, Forensic Medicine and Orthopedics-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.affiliation: Centre of Space Bio-Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palombo
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy ; Italian Space Agency (ASI), Rome, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002364:Caseins / Q000096:biosynthesis; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000473:pathology; D010047:Ovalbumin / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D002364:Caseins; C000715467:KLF4 protein, human; D053538:Keratin-18; D000090062:Kruppel-Like Factor 4; D010047:Ovalbumin