Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

Abstract Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-res...

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Autores principales:	Simona Taverna, Marzia Pucci, Marco Giallombardo, Maria Antonietta Di Bella, Mariacarmela Santarpia, Pablo Reclusa, Ignacio Gil-Bazo, Christian Rolfo, Riccardo Alessandro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/db6a33130d004cc092b9ee22df28e4be
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spelling	oai:doaj.org-article:db6a33130d004cc092b9ee22df28e4be2021-12-02T11:53:02ZAmphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway10.1038/s41598-017-03460-y2045-2322https://doaj.org/article/db6a33130d004cc092b9ee22df28e4be2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03460-yhttps://doaj.org/toc/2045-2322Abstract Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently found as a signaling molecule in exosomes derived from cancer cell lines. Exosomes have a key role in the cell-cell communication and they were recently indicated as important actors in metastatic niche preparation. In the present work, we hypothesize a role of AREG carried by exosomes derived from NSCLC in bone metastasis induction. We observed that NSCLC-exosomes, containing AREG, induce EGFR pathway activation in pre-osteoclasts that in turn causes an increased expression of RANKL. RANKL is able to induce the expression of proteolytic enzymes, well-known markers of osteoclastogenesis, triggering a vicious cycle in osteolytic bone metastasis.Simona TavernaMarzia PucciMarco GiallombardoMaria Antonietta Di BellaMariacarmela SantarpiaPablo ReclusaIgnacio Gil-BazoChristian RolfoRiccardo AlessandroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simona Taverna Marzia Pucci Marco Giallombardo Maria Antonietta Di Bella Mariacarmela Santarpia Pablo Reclusa Ignacio Gil-Bazo Christian Rolfo Riccardo Alessandro Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
description	Abstract Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently found as a signaling molecule in exosomes derived from cancer cell lines. Exosomes have a key role in the cell-cell communication and they were recently indicated as important actors in metastatic niche preparation. In the present work, we hypothesize a role of AREG carried by exosomes derived from NSCLC in bone metastasis induction. We observed that NSCLC-exosomes, containing AREG, induce EGFR pathway activation in pre-osteoclasts that in turn causes an increased expression of RANKL. RANKL is able to induce the expression of proteolytic enzymes, well-known markers of osteoclastogenesis, triggering a vicious cycle in osteolytic bone metastasis.
format	article
author	Simona Taverna Marzia Pucci Marco Giallombardo Maria Antonietta Di Bella Mariacarmela Santarpia Pablo Reclusa Ignacio Gil-Bazo Christian Rolfo Riccardo Alessandro
author_facet	Simona Taverna Marzia Pucci Marco Giallombardo Maria Antonietta Di Bella Mariacarmela Santarpia Pablo Reclusa Ignacio Gil-Bazo Christian Rolfo Riccardo Alessandro
author_sort	Simona Taverna
title	Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
title_short	Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
title_full	Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
title_fullStr	Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
title_full_unstemmed	Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway
title_sort	amphiregulin contained in nsclc-exosomes induces osteoclast differentiation through the activation of egfr pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/db6a33130d004cc092b9ee22df28e4be
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Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

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