Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling

Development of resistance represents a major drawback in osteosarcoma treatment, despite improvements in overall survival. Treatment failure and tumor progression have been attributed to pre-existing drug-resistant clones commonly assigned to a cancer stem-like phenotype. Evidence suggests that non...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2016-01, Vol.370 (2), p.286
Main Authors: Martins-Neves, Sara R, Paiva-Oliveira, Daniela I, Wijers-Koster, Pauline M, Abrunhosa, Antero J, Fontes-Ribeiro, Carlos, Bovée, Judith VMG, Cleton-Jansen, Anne-Marie, Gomes, Célia MF
Format: Article
Language:English
Subjects:
Binding sites
Cancer therapies
Chemotherapy
Gene expression
Genomics
Genotype & phenotype
Hypotheses
Medical prognosis
Metastasis
Software
Stem cells
Survival analysis
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page
container_issue 2
container_start_page 286
container_title Cancer letters
container_volume 370
creator Martins-Neves, Sara R
Paiva-Oliveira, Daniela I
Wijers-Koster, Pauline M
Abrunhosa, Antero J
Fontes-Ribeiro, Carlos
Bovée, Judith VMG
Cleton-Jansen, Anne-Marie
Gomes, Célia MF
description Development of resistance represents a major drawback in osteosarcoma treatment, despite improvements in overall survival. Treatment failure and tumor progression have been attributed to pre-existing drug-resistant clones commonly assigned to a cancer stem-like phenotype. Evidence suggests that non stem-like cells, when submitted to certain microenvironmental stimuli, can acquire a stemness phenotype thereby strengthening their capacity to handle with stressful conditions. Here, using osteosarcoma cell lines and a mouse xenograft model, we show that exposure to conventional chemotherapeutics induces a phenotypic cell transition toward a stem-like phenotype. This associates with activation of Wnt/β-catenin signaling, up-regulation of pluripotency factors and detoxification systems (ABC transporters and Aldefluor activity) that ultimately leads to chemotherapy failure. Wnt/β-catenin inhibition combined with doxorubicin, in the MNNG-HOS cells, prevented the up-regulation of factors linked to transition into a stem-like state and can be envisaged as a way to overcome adaptive resistance. Finally, the analysis of the public R2 database, containing microarray data information from diverse osteosarcoma tissues, revealed a correlation between expression of stemness markers and a worse response to chemotherapy, which provides evidence for drug-induced phenotypic stem cell state transitions in osteosarcoma.
doi_str_mv 10.1016/j.canlet.2015.11.013
format article
fullrecord <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_journals_1746598932</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3888237251</sourcerecordid><originalsourceid>FETCH-proquest_journals_17465989323</originalsourceid><addsrcrecordid>eNqNy81KxDAUBeAgCtafN3ARcN3MTdNM2_Wg-ADCLESGGG_blDQZc1PBtzcLH8DV4Ry-w9iDBCFB7neLsCZ4zKIBqYWUAqS6YJXsu6buhh4uWQUK2lr1Sl-zG6IFAHTb6YqNhxnXmGdM5vzDXfjcLBKnjGtAojLwWEokk2xcDbfoPfE8p7hNMzc2u2-TXSxq5MeQd28fmM17bU3GUL7kpmC8C9MduxqNJ7z_y1v2-Pz0enipzyl-bUj5tMQtFUsn2bV7PfSDatT_1C9nGlCo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1746598932</pqid></control><display><type>article</type><title>Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling</title><source>ScienceDirect Journals</source><creator>Martins-Neves, Sara R ; Paiva-Oliveira, Daniela I ; Wijers-Koster, Pauline M ; Abrunhosa, Antero J ; Fontes-Ribeiro, Carlos ; Bovée, Judith VMG ; Cleton-Jansen, Anne-Marie ; Gomes, Célia MF</creator><creatorcontrib>Martins-Neves, Sara R ; Paiva-Oliveira, Daniela I ; Wijers-Koster, Pauline M ; Abrunhosa, Antero J ; Fontes-Ribeiro, Carlos ; Bovée, Judith VMG ; Cleton-Jansen, Anne-Marie ; Gomes, Célia MF</creatorcontrib><description>Development of resistance represents a major drawback in osteosarcoma treatment, despite improvements in overall survival. Treatment failure and tumor progression have been attributed to pre-existing drug-resistant clones commonly assigned to a cancer stem-like phenotype. Evidence suggests that non stem-like cells, when submitted to certain microenvironmental stimuli, can acquire a stemness phenotype thereby strengthening their capacity to handle with stressful conditions. Here, using osteosarcoma cell lines and a mouse xenograft model, we show that exposure to conventional chemotherapeutics induces a phenotypic cell transition toward a stem-like phenotype. This associates with activation of Wnt/β-catenin signaling, up-regulation of pluripotency factors and detoxification systems (ABC transporters and Aldefluor activity) that ultimately leads to chemotherapy failure. Wnt/β-catenin inhibition combined with doxorubicin, in the MNNG-HOS cells, prevented the up-regulation of factors linked to transition into a stem-like state and can be envisaged as a way to overcome adaptive resistance. Finally, the analysis of the public R2 database, containing microarray data information from diverse osteosarcoma tissues, revealed a correlation between expression of stemness markers and a worse response to chemotherapy, which provides evidence for drug-induced phenotypic stem cell state transitions in osteosarcoma.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2015.11.013</identifier><language>eng</language><publisher>Clare: Elsevier Limited</publisher><subject>Binding sites ; Cancer therapies ; Chemotherapy ; Gene expression ; Genomics ; Genotype &amp; phenotype ; Hypotheses ; Medical prognosis ; Metastasis ; Software ; Stem cells ; Survival analysis ; Tumors</subject><ispartof>Cancer letters, 2016-01, Vol.370 (2), p.286</ispartof><rights>Copyright Elsevier Limited Jan 28, 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids></links><search><creatorcontrib>Martins-Neves, Sara R</creatorcontrib><creatorcontrib>Paiva-Oliveira, Daniela I</creatorcontrib><creatorcontrib>Wijers-Koster, Pauline M</creatorcontrib><creatorcontrib>Abrunhosa, Antero J</creatorcontrib><creatorcontrib>Fontes-Ribeiro, Carlos</creatorcontrib><creatorcontrib>Bovée, Judith VMG</creatorcontrib><creatorcontrib>Cleton-Jansen, Anne-Marie</creatorcontrib><creatorcontrib>Gomes, Célia MF</creatorcontrib><title>Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling</title><title>Cancer letters</title><description>Development of resistance represents a major drawback in osteosarcoma treatment, despite improvements in overall survival. Treatment failure and tumor progression have been attributed to pre-existing drug-resistant clones commonly assigned to a cancer stem-like phenotype. Evidence suggests that non stem-like cells, when submitted to certain microenvironmental stimuli, can acquire a stemness phenotype thereby strengthening their capacity to handle with stressful conditions. Here, using osteosarcoma cell lines and a mouse xenograft model, we show that exposure to conventional chemotherapeutics induces a phenotypic cell transition toward a stem-like phenotype. This associates with activation of Wnt/β-catenin signaling, up-regulation of pluripotency factors and detoxification systems (ABC transporters and Aldefluor activity) that ultimately leads to chemotherapy failure. Wnt/β-catenin inhibition combined with doxorubicin, in the MNNG-HOS cells, prevented the up-regulation of factors linked to transition into a stem-like state and can be envisaged as a way to overcome adaptive resistance. Finally, the analysis of the public R2 database, containing microarray data information from diverse osteosarcoma tissues, revealed a correlation between expression of stemness markers and a worse response to chemotherapy, which provides evidence for drug-induced phenotypic stem cell state transitions in osteosarcoma.</description><subject>Binding sites</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Genotype &amp; phenotype</subject><subject>Hypotheses</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Software</subject><subject>Stem cells</subject><subject>Survival analysis</subject><subject>Tumors</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNy81KxDAUBeAgCtafN3ARcN3MTdNM2_Wg-ADCLESGGG_blDQZc1PBtzcLH8DV4Ry-w9iDBCFB7neLsCZ4zKIBqYWUAqS6YJXsu6buhh4uWQUK2lr1Sl-zG6IFAHTb6YqNhxnXmGdM5vzDXfjcLBKnjGtAojLwWEokk2xcDbfoPfE8p7hNMzc2u2-TXSxq5MeQd28fmM17bU3GUL7kpmC8C9MduxqNJ7z_y1v2-Pz0enipzyl-bUj5tMQtFUsn2bV7PfSDatT_1C9nGlCo</recordid><startdate>20160128</startdate><enddate>20160128</enddate><creator>Martins-Neves, Sara R</creator><creator>Paiva-Oliveira, Daniela I</creator><creator>Wijers-Koster, Pauline M</creator><creator>Abrunhosa, Antero J</creator><creator>Fontes-Ribeiro, Carlos</creator><creator>Bovée, Judith VMG</creator><creator>Cleton-Jansen, Anne-Marie</creator><creator>Gomes, Célia MF</creator><general>Elsevier Limited</general><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20160128</creationdate><title>Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling</title><author>Martins-Neves, Sara R ; Paiva-Oliveira, Daniela I ; Wijers-Koster, Pauline M ; Abrunhosa, Antero J ; Fontes-Ribeiro, Carlos ; Bovée, Judith VMG ; Cleton-Jansen, Anne-Marie ; Gomes, Célia MF</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_17465989323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Binding sites</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Genotype &amp; phenotype</topic><topic>Hypotheses</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Software</topic><topic>Stem cells</topic><topic>Survival analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martins-Neves, Sara R</creatorcontrib><creatorcontrib>Paiva-Oliveira, Daniela I</creatorcontrib><creatorcontrib>Wijers-Koster, Pauline M</creatorcontrib><creatorcontrib>Abrunhosa, Antero J</creatorcontrib><creatorcontrib>Fontes-Ribeiro, Carlos</creatorcontrib><creatorcontrib>Bovée, Judith VMG</creatorcontrib><creatorcontrib>Cleton-Jansen, Anne-Marie</creatorcontrib><creatorcontrib>Gomes, Célia MF</creatorcontrib><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martins-Neves, Sara R</au><au>Paiva-Oliveira, Daniela I</au><au>Wijers-Koster, Pauline M</au><au>Abrunhosa, Antero J</au><au>Fontes-Ribeiro, Carlos</au><au>Bovée, Judith VMG</au><au>Cleton-Jansen, Anne-Marie</au><au>Gomes, Célia MF</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling</atitle><jtitle>Cancer letters</jtitle><date>2016-01-28</date><risdate>2016</risdate><volume>370</volume><issue>2</issue><spage>286</spage><pages>286-</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Development of resistance represents a major drawback in osteosarcoma treatment, despite improvements in overall survival. Treatment failure and tumor progression have been attributed to pre-existing drug-resistant clones commonly assigned to a cancer stem-like phenotype. Evidence suggests that non stem-like cells, when submitted to certain microenvironmental stimuli, can acquire a stemness phenotype thereby strengthening their capacity to handle with stressful conditions. Here, using osteosarcoma cell lines and a mouse xenograft model, we show that exposure to conventional chemotherapeutics induces a phenotypic cell transition toward a stem-like phenotype. This associates with activation of Wnt/β-catenin signaling, up-regulation of pluripotency factors and detoxification systems (ABC transporters and Aldefluor activity) that ultimately leads to chemotherapy failure. Wnt/β-catenin inhibition combined with doxorubicin, in the MNNG-HOS cells, prevented the up-regulation of factors linked to transition into a stem-like state and can be envisaged as a way to overcome adaptive resistance. Finally, the analysis of the public R2 database, containing microarray data information from diverse osteosarcoma tissues, revealed a correlation between expression of stemness markers and a worse response to chemotherapy, which provides evidence for drug-induced phenotypic stem cell state transitions in osteosarcoma.</abstract><cop>Clare</cop><pub>Elsevier Limited</pub><doi>10.1016/j.canlet.2015.11.013</doi></addata></record>
fulltext fulltext
identifier ISSN: 0304-3835
ispartof Cancer letters, 2016-01, Vol.370 (2), p.286
issn 0304-3835
1872-7980
language eng
recordid cdi_proquest_journals_1746598932
source ScienceDirect Journals
subjects Binding sites
Cancer therapies
Chemotherapy
Gene expression
Genomics
Genotype & phenotype
Hypotheses
Medical prognosis
Metastasis
Software
Stem cells
Survival analysis
Tumors
title Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/[beta]-catenin signaling
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-23T03%3A18%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chemotherapy%20induces%20stemness%20in%20osteosarcoma%20cells%20through%20activation%20of%20Wnt/%5Bbeta%5D-catenin%20signaling&rft.jtitle=Cancer%20letters&rft.au=Martins-Neves,%20Sara%20R&rft.date=2016-01-28&rft.volume=370&rft.issue=2&rft.spage=286&rft.pages=286-&rft.issn=0304-3835&rft.eissn=1872-7980&rft_id=info:doi/10.1016/j.canlet.2015.11.013&rft_dat=%3Cproquest%3E3888237251%3C/proquest%3E%3Cgrp_id%3Ecdi_FETCH-proquest_journals_17465989323%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1746598932&rft_id=info:pmid/&rfr_iscdi=true