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Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment

Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, and young adults. Despite encouraging progress in therapeutic management, including the advent of multidrug chemotherapy, the survival rates have remained unchanged for more than four decades: 75...

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Autores principales: Verrecchia, Franck, Rédini, Françoise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937053/
https://www.ncbi.nlm.nih.gov/pubmed/29761075
http://dx.doi.org/10.3389/fonc.2018.00133
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author Verrecchia, Franck
Rédini, Françoise
author_facet Verrecchia, Franck
Rédini, Françoise
author_sort Verrecchia, Franck
collection PubMed
description Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, and young adults. Despite encouraging progress in therapeutic management, including the advent of multidrug chemotherapy, the survival rates have remained unchanged for more than four decades: 75% at 5 years for localized disease, but two groups of patients are still at high risk: metastatic at diagnosis (overall survival around 40% at 5 years) and/or poor responders to chemotherapy (20% at 5 years). Because these tumors are classified as “complex genomic,” it is extremely difficult to determine the signaling pathways that might be targeted by specific therapies. A hypothesis has thus emerged, stating that the particular microenvironment of these tumors may interfere with the tumor cells that promote chemoresistance and the dissemination of metastases. The stroma is composed of a large number of cell types (immune cells, endothelial cells, mesenchymal stromal cells, etc.) which secrete growth factors, such as transforming growth factor-β (TGF-β), which favors the development of primary tumors and dissemination of metastases by constituting a permissive niche at primary and distant sites. Rather than targeting the tumor cells themselves, which are very heterogeneous in osteosarcoma, the hypothesis is instead to target the key actors secreted in the microenvironment, such as TGF-βs, which play a part in tumor progression. In the last decade, numerous studies have shown that overexpression of TGF-β is a hallmark of many cancers, including primary bone tumors. In this context, TGF-β signaling has emerged as a crucial factor in the cross talk between tumor cells and stroma cells in poor-prognosis cancers. Secretion of TGF-β by tumor cells or stroma cells can effectively act in a paracrine manner to regulate the phenotype and functions of the microenvironment to stimulate protumorigenic microenvironmental changes. TGF-β can thus exert its protumorigenic function in primary bone tumors by promoting angiogenesis, bone remodeling and cell migration, and by inhibiting immunosurveillance. This review focuses on the involvement of TGF-β signaling in primary bone tumor development, and the related therapeutic options that may be possible for these tumors.
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spelling pubmed-59370532018-05-14 Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment Verrecchia, Franck Rédini, Françoise Front Oncol Oncology Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, and young adults. Despite encouraging progress in therapeutic management, including the advent of multidrug chemotherapy, the survival rates have remained unchanged for more than four decades: 75% at 5 years for localized disease, but two groups of patients are still at high risk: metastatic at diagnosis (overall survival around 40% at 5 years) and/or poor responders to chemotherapy (20% at 5 years). Because these tumors are classified as “complex genomic,” it is extremely difficult to determine the signaling pathways that might be targeted by specific therapies. A hypothesis has thus emerged, stating that the particular microenvironment of these tumors may interfere with the tumor cells that promote chemoresistance and the dissemination of metastases. The stroma is composed of a large number of cell types (immune cells, endothelial cells, mesenchymal stromal cells, etc.) which secrete growth factors, such as transforming growth factor-β (TGF-β), which favors the development of primary tumors and dissemination of metastases by constituting a permissive niche at primary and distant sites. Rather than targeting the tumor cells themselves, which are very heterogeneous in osteosarcoma, the hypothesis is instead to target the key actors secreted in the microenvironment, such as TGF-βs, which play a part in tumor progression. In the last decade, numerous studies have shown that overexpression of TGF-β is a hallmark of many cancers, including primary bone tumors. In this context, TGF-β signaling has emerged as a crucial factor in the cross talk between tumor cells and stroma cells in poor-prognosis cancers. Secretion of TGF-β by tumor cells or stroma cells can effectively act in a paracrine manner to regulate the phenotype and functions of the microenvironment to stimulate protumorigenic microenvironmental changes. TGF-β can thus exert its protumorigenic function in primary bone tumors by promoting angiogenesis, bone remodeling and cell migration, and by inhibiting immunosurveillance. This review focuses on the involvement of TGF-β signaling in primary bone tumor development, and the related therapeutic options that may be possible for these tumors. Frontiers Media S.A. 2018-04-30 /pmc/articles/PMC5937053/ /pubmed/29761075 http://dx.doi.org/10.3389/fonc.2018.00133 Text en Copyright © 2018 Verrecchia and Rédini. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Verrecchia, Franck
Rédini, Françoise
Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title_full Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title_fullStr Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title_full_unstemmed Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title_short Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment
title_sort transforming growth factor-β signaling plays a pivotal role in the interplay between osteosarcoma cells and their microenvironment
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937053/
https://www.ncbi.nlm.nih.gov/pubmed/29761075
http://dx.doi.org/10.3389/fonc.2018.00133
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