A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells
•Chondrosarcoma stem cells (ChSCs) are radioresistant and are suppressed by miR-34.•mTOR inhibition by Rapamycin targets ChSCs via FOXO3 and miR-34.•Combination of carbon-ion therapy with mTOR inhibitors effectively controls ChSCs. High-grade chondrosarcomas are chemo- and radio-resistant cartilage-...
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| Veröffentlicht in: | Radiotherapy and oncology 2020-09, Vol.150, p.253-261 |
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| creator | Vares, Guillaume Ahire, Vidhula Sunada, Shigeaki Ho Kim, Eun Sai, Sei Chevalier, François Romeo, Paul-Henri Yamamoto, Tadashi Nakajima, Tetsuo Saintigny, Yannick |
| description | •Chondrosarcoma stem cells (ChSCs) are radioresistant and are suppressed by miR-34.•mTOR inhibition by Rapamycin targets ChSCs via FOXO3 and miR-34.•Combination of carbon-ion therapy with mTOR inhibitors effectively controls ChSCs.
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma. |
| doi_str_mv | 10.1016/j.radonc.2020.07.034 |
| format | Article |
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High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.</description><identifier>ISSN: 0167-8140</identifier><identifier>EISSN: 1879-0887</identifier><identifier>DOI: 10.1016/j.radonc.2020.07.034</identifier><identifier>PMID: 32717360</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Biochemistry, Molecular Biology ; Biological Physics ; Bone Neoplasms - radiotherapy ; Cancer ; Cancer stem cell ; Carbon ; Cell Line, Tumor ; Cellular Biology ; Chondrosarcoma ; Chondrosarcoma - genetics ; Chondrosarcoma - therapy ; Combined Modality Therapy ; Genomics ; Humans ; Ions ; Life Sciences ; MicroRNAs - genetics ; miR-34 ; mTOR inhibitor ; Neoplasm Recurrence, Local ; Neoplastic Stem Cells ; Particle therapy ; Physics ; TOR Serine-Threonine Kinases</subject><ispartof>Radiotherapy and oncology, 2020-09, Vol.150, p.253-261</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-291e94605cf1fe86366c81785bff7d3f511ed89d13d16b64b480243cda7feeda3</citedby><cites>FETCH-LOGICAL-c486t-291e94605cf1fe86366c81785bff7d3f511ed89d13d16b64b480243cda7feeda3</cites><orcidid>0000-0002-3839-3562 ; 0000-0002-9446-8522 ; 0000-0002-8488-2324 ; 0000-0002-6191-9032</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.radonc.2020.07.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32717360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03298410$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vares, Guillaume</creatorcontrib><creatorcontrib>Ahire, Vidhula</creatorcontrib><creatorcontrib>Sunada, Shigeaki</creatorcontrib><creatorcontrib>Ho Kim, Eun</creatorcontrib><creatorcontrib>Sai, Sei</creatorcontrib><creatorcontrib>Chevalier, François</creatorcontrib><creatorcontrib>Romeo, Paul-Henri</creatorcontrib><creatorcontrib>Yamamoto, Tadashi</creatorcontrib><creatorcontrib>Nakajima, Tetsuo</creatorcontrib><creatorcontrib>Saintigny, Yannick</creatorcontrib><title>A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells</title><title>Radiotherapy and oncology</title><addtitle>Radiother Oncol</addtitle><description>•Chondrosarcoma stem cells (ChSCs) are radioresistant and are suppressed by miR-34.•mTOR inhibition by Rapamycin targets ChSCs via FOXO3 and miR-34.•Combination of carbon-ion therapy with mTOR inhibitors effectively controls ChSCs.
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.</description><subject>Biochemistry, Molecular Biology</subject><subject>Biological Physics</subject><subject>Bone Neoplasms - radiotherapy</subject><subject>Cancer</subject><subject>Cancer stem cell</subject><subject>Carbon</subject><subject>Cell Line, Tumor</subject><subject>Cellular Biology</subject><subject>Chondrosarcoma</subject><subject>Chondrosarcoma - genetics</subject><subject>Chondrosarcoma - therapy</subject><subject>Combined Modality Therapy</subject><subject>Genomics</subject><subject>Humans</subject><subject>Ions</subject><subject>Life Sciences</subject><subject>MicroRNAs - genetics</subject><subject>miR-34</subject><subject>mTOR inhibitor</subject><subject>Neoplasm Recurrence, Local</subject><subject>Neoplastic Stem Cells</subject><subject>Particle therapy</subject><subject>Physics</subject><subject>TOR Serine-Threonine Kinases</subject><issn>0167-8140</issn><issn>1879-0887</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFqHCEUhqU0NNukb1CKt4XOREd3dG4KS2ibwtJASK7F0WPGZdTFMYE8RV-5LtPmsleifN85x_Mj9JGSlhLaXx3arG2Kpu1IR1oiWsL4G7ShUgwNkVK8RZuKiUZSTs7R-2U5EFJJJt6hc9YJKlhPNuj3DoenufiQrJ5xyaBLgFhwctjoPKaIfYoL9rk287rUyxcc_N2vXcM41tHicH97h32c_OhLyng5gvHOGz3PL9ikWHKa8eQfp-axVgBsphRtTovOJgVde0QD1SoQsIF5Xi7RmdPzAh_-nhfo4fu3--ubZn_74-f1bt8YLvvSdAOFgfdkaxx1IHvW90ZSIbejc8Iyt6UUrBwsZZb2Y89HLknHmbFaOACr2QX6vNad9KyO2QedX1TSXt3s9ur0Rlg3SE7JM60sX1lTB18yuFeBEnXKQh3UmoU6ZaGIqDav2qdVOz6NAeyr9G_5Ffi6AlA_-uwhq8V4qAuxPoMpyib__w5_AGeFnig</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Vares, Guillaume</creator><creator>Ahire, Vidhula</creator><creator>Sunada, Shigeaki</creator><creator>Ho Kim, Eun</creator><creator>Sai, Sei</creator><creator>Chevalier, François</creator><creator>Romeo, Paul-Henri</creator><creator>Yamamoto, Tadashi</creator><creator>Nakajima, Tetsuo</creator><creator>Saintigny, Yannick</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3839-3562</orcidid><orcidid>https://orcid.org/0000-0002-9446-8522</orcidid><orcidid>https://orcid.org/0000-0002-8488-2324</orcidid><orcidid>https://orcid.org/0000-0002-6191-9032</orcidid></search><sort><creationdate>20200901</creationdate><title>A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells</title><author>Vares, Guillaume ; Ahire, Vidhula ; Sunada, Shigeaki ; Ho Kim, Eun ; Sai, Sei ; Chevalier, François ; Romeo, Paul-Henri ; Yamamoto, Tadashi ; Nakajima, Tetsuo ; Saintigny, Yannick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-291e94605cf1fe86366c81785bff7d3f511ed89d13d16b64b480243cda7feeda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biochemistry, Molecular Biology</topic><topic>Biological Physics</topic><topic>Bone Neoplasms - radiotherapy</topic><topic>Cancer</topic><topic>Cancer stem cell</topic><topic>Carbon</topic><topic>Cell Line, Tumor</topic><topic>Cellular Biology</topic><topic>Chondrosarcoma</topic><topic>Chondrosarcoma - genetics</topic><topic>Chondrosarcoma - therapy</topic><topic>Combined Modality Therapy</topic><topic>Genomics</topic><topic>Humans</topic><topic>Ions</topic><topic>Life Sciences</topic><topic>MicroRNAs - genetics</topic><topic>miR-34</topic><topic>mTOR inhibitor</topic><topic>Neoplasm Recurrence, Local</topic><topic>Neoplastic Stem Cells</topic><topic>Particle therapy</topic><topic>Physics</topic><topic>TOR Serine-Threonine Kinases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vares, Guillaume</creatorcontrib><creatorcontrib>Ahire, Vidhula</creatorcontrib><creatorcontrib>Sunada, Shigeaki</creatorcontrib><creatorcontrib>Ho Kim, Eun</creatorcontrib><creatorcontrib>Sai, Sei</creatorcontrib><creatorcontrib>Chevalier, François</creatorcontrib><creatorcontrib>Romeo, Paul-Henri</creatorcontrib><creatorcontrib>Yamamoto, Tadashi</creatorcontrib><creatorcontrib>Nakajima, Tetsuo</creatorcontrib><creatorcontrib>Saintigny, Yannick</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Radiotherapy and oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vares, Guillaume</au><au>Ahire, Vidhula</au><au>Sunada, Shigeaki</au><au>Ho Kim, Eun</au><au>Sai, Sei</au><au>Chevalier, François</au><au>Romeo, Paul-Henri</au><au>Yamamoto, Tadashi</au><au>Nakajima, Tetsuo</au><au>Saintigny, Yannick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells</atitle><jtitle>Radiotherapy and oncology</jtitle><addtitle>Radiother Oncol</addtitle><date>2020-09-01</date><risdate>2020</risdate><volume>150</volume><spage>253</spage><epage>261</epage><pages>253-261</pages><issn>0167-8140</issn><eissn>1879-0887</eissn><abstract>•Chondrosarcoma stem cells (ChSCs) are radioresistant and are suppressed by miR-34.•mTOR inhibition by Rapamycin targets ChSCs via FOXO3 and miR-34.•Combination of carbon-ion therapy with mTOR inhibitors effectively controls ChSCs.
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>32717360</pmid><doi>10.1016/j.radonc.2020.07.034</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3839-3562</orcidid><orcidid>https://orcid.org/0000-0002-9446-8522</orcidid><orcidid>https://orcid.org/0000-0002-8488-2324</orcidid><orcidid>https://orcid.org/0000-0002-6191-9032</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-8140 |
| ispartof | Radiotherapy and oncology, 2020-09, Vol.150, p.253-261 |
| issn | 0167-8140 1879-0887 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Biochemistry, Molecular Biology Biological Physics Bone Neoplasms - radiotherapy Cancer Cancer stem cell Carbon Cell Line, Tumor Cellular Biology Chondrosarcoma Chondrosarcoma - genetics Chondrosarcoma - therapy Combined Modality Therapy Genomics Humans Ions Life Sciences MicroRNAs - genetics miR-34 mTOR inhibitor Neoplasm Recurrence, Local Neoplastic Stem Cells Particle therapy Physics TOR Serine-Threonine Kinases |
| title | A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells |
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