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The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases

Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis...

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Autores principales: Navet, Benjamin, Ando, Kosei, Vargas-Franco, Jorge William, Brion, Régis, Amiaud, Jérome, Mori, Kanji, Yagita, Hideo, Mueller, Christopher G., Verrecchia, Franck, Dumars, Clotilde, Heymann, Marie-Françoise, Heymann, Dominique, Lézot, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265790/
https://www.ncbi.nlm.nih.gov/pubmed/30355966
http://dx.doi.org/10.3390/cancers10110398
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author Navet, Benjamin
Ando, Kosei
Vargas-Franco, Jorge William
Brion, Régis
Amiaud, Jérome
Mori, Kanji
Yagita, Hideo
Mueller, Christopher G.
Verrecchia, Franck
Dumars, Clotilde
Heymann, Marie-Françoise
Heymann, Dominique
Lézot, Frédéric
author_facet Navet, Benjamin
Ando, Kosei
Vargas-Franco, Jorge William
Brion, Régis
Amiaud, Jérome
Mori, Kanji
Yagita, Hideo
Mueller, Christopher G.
Verrecchia, Franck
Dumars, Clotilde
Heymann, Marie-Françoise
Heymann, Dominique
Lézot, Frédéric
author_sort Navet, Benjamin
collection PubMed
description Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.
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spelling pubmed-62657902018-12-03 The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases Navet, Benjamin Ando, Kosei Vargas-Franco, Jorge William Brion, Régis Amiaud, Jérome Mori, Kanji Yagita, Hideo Mueller, Christopher G. Verrecchia, Franck Dumars, Clotilde Heymann, Marie-Françoise Heymann, Dominique Lézot, Frédéric Cancers (Basel) Article Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma. MDPI 2018-10-24 /pmc/articles/PMC6265790/ /pubmed/30355966 http://dx.doi.org/10.3390/cancers10110398 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Navet, Benjamin
Ando, Kosei
Vargas-Franco, Jorge William
Brion, Régis
Amiaud, Jérome
Mori, Kanji
Yagita, Hideo
Mueller, Christopher G.
Verrecchia, Franck
Dumars, Clotilde
Heymann, Marie-Françoise
Heymann, Dominique
Lézot, Frédéric
The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title_full The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title_fullStr The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title_full_unstemmed The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title_short The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases
title_sort intrinsic and extrinsic implications of rankl/rank signaling in osteosarcoma: from tumor initiation to lung metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265790/
https://www.ncbi.nlm.nih.gov/pubmed/30355966
http://dx.doi.org/10.3390/cancers10110398
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