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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6265790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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