MUC5B silencing reduces chemo-resistance of MCF-7 breast tumor cells and impairs maturation of dendritic cells

García,Enrique P.; Tiscornia,Inés; Libisch,Gabriela; Trajtenberg,Felipe; Bollati-Fogolín,Mariela; Rodríguez,Ernesto; Noya,Verónica; Chiale,Carolina; Brossard,Natalie; Robello,Carlos; Santiñaque,Federico; Folle,Gustavo; Osinaga,Eduardo; Freire,Teresa

doi:10.3892/ijo.2016.3434

MUC5B silencing reduces chemo-resistance of MCF-7 breast tumor cells and impairs maturation of dendritic cells

Authors:
- Enrique P. García
- Inés Tiscornia
- Gabriela Libisch
- Felipe Trajtenberg
- Mariela Bollati-Fogolín
- Ernesto Rodríguez
- Verónica Noya
- Carolina Chiale
- Natalie Brossard
- Carlos Robello
- Federico Santiñaque
- Gustavo Folle
- Eduardo Osinaga
- Teresa Freire
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Affiliations: Department of Immunobiology, Immunomodulation and Vaccine Development Laboratory, Facultad de Medicina, UdelaR, CP11800 Montevideo, Uruguay, Cell Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay, Molecular Biology Unit, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay, Unit of Protein Crystallography, Institut Pasteur de Montevideo, CP 11400 Montevideo, Uruguay, Department of Genetics, Instituto de Investigaciones Biológicas Clemente Estable, CP 11600 Montevideo, Uruguay, Glycobiology and Tumor Immunology Laboratory, Institut Pasteur de Montevideo, CP 11400, Uruguay
Published online on: March 10, 2016 https://doi.org/10.3892/ijo.2016.3434
Pages: 2113-2123

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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.

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