title: MUC5B silencing reduces chemo-resistance of MCF-7 breast tumor cells and impairs maturation of dendritic cells.
abstract: Mucins participate in cancer progression by regulating cell growth, adhesion, signaling, apoptosis or chemo-resistance to drugs. The secreted mucin MUC5B, the major component of the respiratory tract mucus, is aberrantly expressed in breast cancer, where it could constitute a cancer biomarker. In this study we evaluated the role of MUC5B in breast cancer by gene silencing the MUC5B expression with short hairpin RNA on MCF-7 cells. We found that MUC5B-silenced MCF-7 cells have a reduced capacity to grow, adhere and form cell colonies. Interestingly, MUC5B knock-down increased the sensitivity to death induced by chemotherapeutic drugs. We also show that MUC5B silencing impaired LPS-maturation of DCs, and production of cytokines. Furthermore, MUC5B knock-down also influenced DC-differentiation and activation since it resulted in an upregulation of IL-1β, IL-6 and IL-10, cytokines that might be involved in cancer progression. Thus, MUC5B could enhance the production of LPS-induced cytokines, suggesting that the use of MUC5B-based cancer vaccines combined with DC-maturation stimuli, could favor the induction of an antitumor immune response.
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Enrique P
authors.initials: EP
authors.lastname: García
authors.affiliation: Cell Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay.
authors.forename: Inés
authors.initials: I
authors.lastname: Tiscornia
authors.affiliation: Molecular Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Libisch
authors.affiliation: Unit of Protein Crystallography, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay.
authors.forename: Felipe
authors.initials: F
authors.lastname: Trajtenberg
authors.affiliation: Cell Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay.
authors.forename: Mariela
authors.initials: M
authors.lastname: Bollati-Fogolín
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Verónica
authors.initials: V
authors.lastname: Noya
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Carolina
authors.initials: C
authors.lastname: Chiale
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Natalie
authors.initials: N
authors.lastname: Brossard
authors.affiliation: Molecular Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robello
authors.affiliation: Department of Genetics, Instituto de Investigaciones Biológicas Clemente Estable, CP 11600 Montevideo, Uruguay.
authors.forename: Federico
authors.initials: F
authors.lastname: Santiñaque
authors.affiliation: Department of Genetics, Instituto de Investigaciones Biológicas Clemente Estable, CP 11600 Montevideo, Uruguay.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Folle
authors.affiliation: Glycobiology and Tumor Immunology Laboratory, Institut Pasteur de Montevideo, CP 11400, Uruguay.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Osinaga
authors.affiliation: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay.
authors.forename: Teresa
authors.initials: T
authors.lastname: Freire
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D019008:Drug Resistance, Neoplasm; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D061986:MCF-7 Cells; D055257:Mucin-5B / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C524578:MUC5B protein, human; D055257:Mucin-5B