MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma

Abstract Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. Resistance to chemotherapy remains a key challenge for effective treatment of patients with osteosarcoma. The aim of the present study was to investigate the preventive role of metallothionein-2A (MT2A)...

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Autores principales:	Adèle Mangelinck, Maria Eugénia Marques da Costa, Bojana Stefanovska, Olivia Bawa, Mélanie Polrot, Nathalie Gaspar, Olivia Fromigué
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22d185a0684f4e9a8d8e736977224818
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spelling	oai:doaj.org-article:22d185a0684f4e9a8d8e7369772248182021-12-02T15:08:08ZMT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma10.1038/s41598-019-48846-22045-2322https://doaj.org/article/22d185a0684f4e9a8d8e7369772248182019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48846-2https://doaj.org/toc/2045-2322Abstract Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. Resistance to chemotherapy remains a key challenge for effective treatment of patients with osteosarcoma. The aim of the present study was to investigate the preventive role of metallothionein-2A (MT2A) in response to cytotoxic effects of chemotherapy. A panel of human and murine osteosarcoma cell lines, modified for MT2A were evaluated for cell viability, and motility (wound healing assay). Cell-derived xenograft models were established in mice. FFPE tumour samples were assessed by IHC. In vitro experiments indicated a positive correlation between half-maximal inhibitory concentration (IC50) for drugs in clinical practice, and MT2A mRNA level. This reinforced our previously reported correlation between MT2A mRNA level in tumour samples at diagnosis and overall survival in patients with osteosarcoma. In addition, MT2A/MT2 silencing using shRNA strategy led to a marked reduction of IC50 values and to enhanced cytotoxic effect of chemotherapy on primary tumour. Our results show that MT2A level could be used as a predictive biomarker of resistance to chemotherapy, and provide with preclinical rational for MT2A targeting as a therapeutic strategy for enhancing anti-tumour treatment of innate chemo-resistant osteosarcoma cells.Adèle MangelinckMaria Eugénia Marques da CostaBojana StefanovskaOlivia BawaMélanie PolrotNathalie GasparOlivia FromiguéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adèle Mangelinck Maria Eugénia Marques da Costa Bojana Stefanovska Olivia Bawa Mélanie Polrot Nathalie Gaspar Olivia Fromigué MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
description	Abstract Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. Resistance to chemotherapy remains a key challenge for effective treatment of patients with osteosarcoma. The aim of the present study was to investigate the preventive role of metallothionein-2A (MT2A) in response to cytotoxic effects of chemotherapy. A panel of human and murine osteosarcoma cell lines, modified for MT2A were evaluated for cell viability, and motility (wound healing assay). Cell-derived xenograft models were established in mice. FFPE tumour samples were assessed by IHC. In vitro experiments indicated a positive correlation between half-maximal inhibitory concentration (IC50) for drugs in clinical practice, and MT2A mRNA level. This reinforced our previously reported correlation between MT2A mRNA level in tumour samples at diagnosis and overall survival in patients with osteosarcoma. In addition, MT2A/MT2 silencing using shRNA strategy led to a marked reduction of IC50 values and to enhanced cytotoxic effect of chemotherapy on primary tumour. Our results show that MT2A level could be used as a predictive biomarker of resistance to chemotherapy, and provide with preclinical rational for MT2A targeting as a therapeutic strategy for enhancing anti-tumour treatment of innate chemo-resistant osteosarcoma cells.
format	article
author	Adèle Mangelinck Maria Eugénia Marques da Costa Bojana Stefanovska Olivia Bawa Mélanie Polrot Nathalie Gaspar Olivia Fromigué
author_facet	Adèle Mangelinck Maria Eugénia Marques da Costa Bojana Stefanovska Olivia Bawa Mélanie Polrot Nathalie Gaspar Olivia Fromigué
author_sort	Adèle Mangelinck
title	MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
title_short	MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
title_full	MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
title_fullStr	MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
title_full_unstemmed	MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
title_sort	mt2a is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/22d185a0684f4e9a8d8e736977224818
work_keys_str_mv	AT adelemangelinck mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT mariaeugeniamarquesdacosta mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT bojanastefanovska mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT oliviabawa mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT melaniepolrot mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT nathaliegaspar mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma AT oliviafromigue mt2aisanearlypredictivebiomarkerofresponsetochemotherapyandapotentialtherapeutictargetinosteosarcoma
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MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma

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