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Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3...

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Autores principales: Franco-Molina, Moisés A, Miranda-Hernández, Diana F, Mendoza-Gamboa, Edgar, Zapata-Benavides, Pablo, Coronado-Cerda, Erika E, Sierra-Rivera, Crystel A, Saavedra-Alonso, Santiago, Taméz-Guerra, Reyes S, Rodríguez-Padilla, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716752/
https://www.ncbi.nlm.nih.gov/pubmed/26834483
http://dx.doi.org/10.2147/OTT.S90476
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author Franco-Molina, Moisés A
Miranda-Hernández, Diana F
Mendoza-Gamboa, Edgar
Zapata-Benavides, Pablo
Coronado-Cerda, Erika E
Sierra-Rivera, Crystel A
Saavedra-Alonso, Santiago
Taméz-Guerra, Reyes S
Rodríguez-Padilla, Cristina
author_facet Franco-Molina, Moisés A
Miranda-Hernández, Diana F
Mendoza-Gamboa, Edgar
Zapata-Benavides, Pablo
Coronado-Cerda, Erika E
Sierra-Rivera, Crystel A
Saavedra-Alonso, Santiago
Taméz-Guerra, Reyes S
Rodríguez-Padilla, Cristina
author_sort Franco-Molina, Moisés A
collection PubMed
description Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25(+) expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25(+) than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4(+) cells (CD4(+), CD4(+)CD25(+), and CD4(+)CD25(+)Foxp3(+)) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment.
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spelling pubmed-47167522016-02-01 Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment Franco-Molina, Moisés A Miranda-Hernández, Diana F Mendoza-Gamboa, Edgar Zapata-Benavides, Pablo Coronado-Cerda, Erika E Sierra-Rivera, Crystel A Saavedra-Alonso, Santiago Taméz-Guerra, Reyes S Rodríguez-Padilla, Cristina Onco Targets Ther Original Research Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25(+) expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25(+) than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4(+) cells (CD4(+), CD4(+)CD25(+), and CD4(+)CD25(+)Foxp3(+)) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment. Dove Medical Press 2016-01-12 /pmc/articles/PMC4716752/ /pubmed/26834483 http://dx.doi.org/10.2147/OTT.S90476 Text en © 2016 Franco-Molina et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Franco-Molina, Moisés A
Miranda-Hernández, Diana F
Mendoza-Gamboa, Edgar
Zapata-Benavides, Pablo
Coronado-Cerda, Erika E
Sierra-Rivera, Crystel A
Saavedra-Alonso, Santiago
Taméz-Guerra, Reyes S
Rodríguez-Padilla, Cristina
Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title_full Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title_fullStr Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title_full_unstemmed Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title_short Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
title_sort silencing of foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716752/
https://www.ncbi.nlm.nih.gov/pubmed/26834483
http://dx.doi.org/10.2147/OTT.S90476
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