CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression
In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐b...
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| Veröffentlicht in: | Journal of cellular physiology 2019-06, Vol.234 (6), p.9297-9307 |
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| creator | Tsai, Hsiao‐Chi Chang, An‐Chen Tsai, Chun‐Hao Huang, Yuan‐Li Gan, Lijun Chen, Chi‐Kuan Liu, Shih‐Chia Huang, Te‐Yang Fong, Yi‐Chin Tang, Chih‐Hsin |
| description | In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.
Chemoresistance is an important problem in osteosarcoma. CCN2 promotes drug resistance in osteosarcoma. CCN2 increases ABCG2 protein expression and activation in osteosarcoma |
| doi_str_mv | 10.1002/jcp.27611 |
| format | Article |
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Chemoresistance is an important problem in osteosarcoma. CCN2 promotes drug resistance in osteosarcoma. CCN2 increases ABCG2 protein expression and activation in osteosarcoma</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.27611</identifier><identifier>PMID: 30317661</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>ABCG2 ; Animals ; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics ; Base Sequence ; Binding ; Biocompatibility ; Bone cancer ; Breast cancer ; Cancer ; CCN2 ; Cell Line, Tumor ; Cell Survival - genetics ; Chemoresistance ; chemotherapeutic resistance ; Connective tissue growth factor ; Connective Tissue Growth Factor - metabolism ; Doxorubicin ; Drug resistance ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Humans ; Integrin alpha6beta1 - metabolism ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Models, Biological ; Neoplasm Proteins - genetics ; Osteosarcoma ; Osteosarcoma - genetics ; Proteins ; Sarcoma ; Signal Transduction ; Survival ; Xenobiotics ; Xenografts ; Xenotransplantation</subject><ispartof>Journal of cellular physiology, 2019-06, Vol.234 (6), p.9297-9307</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-1456239d3482257aa65153f5875e2b1a140e986f4af663496286f3ac9646f5c43</citedby><cites>FETCH-LOGICAL-c3531-1456239d3482257aa65153f5875e2b1a140e986f4af663496286f3ac9646f5c43</cites><orcidid>0000-0002-3405-8863 ; 0000-0002-7113-8352</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.27611$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.27611$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30317661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Hsiao‐Chi</creatorcontrib><creatorcontrib>Chang, An‐Chen</creatorcontrib><creatorcontrib>Tsai, Chun‐Hao</creatorcontrib><creatorcontrib>Huang, Yuan‐Li</creatorcontrib><creatorcontrib>Gan, Lijun</creatorcontrib><creatorcontrib>Chen, Chi‐Kuan</creatorcontrib><creatorcontrib>Liu, Shih‐Chia</creatorcontrib><creatorcontrib>Huang, Te‐Yang</creatorcontrib><creatorcontrib>Fong, Yi‐Chin</creatorcontrib><creatorcontrib>Tang, Chih‐Hsin</creatorcontrib><title>CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.
Chemoresistance is an important problem in osteosarcoma. CCN2 promotes drug resistance in osteosarcoma. CCN2 increases ABCG2 protein expression and activation in osteosarcoma</description><subject>ABCG2</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics</subject><subject>Base Sequence</subject><subject>Binding</subject><subject>Biocompatibility</subject><subject>Bone cancer</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>CCN2</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - genetics</subject><subject>Chemoresistance</subject><subject>chemotherapeutic resistance</subject><subject>Connective tissue growth factor</subject><subject>Connective Tissue Growth Factor - metabolism</subject><subject>Doxorubicin</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Integrin alpha6beta1 - metabolism</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Models, Biological</subject><subject>Neoplasm Proteins - genetics</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - genetics</subject><subject>Proteins</subject><subject>Sarcoma</subject><subject>Signal Transduction</subject><subject>Survival</subject><subject>Xenobiotics</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10LtOwzAUBmALgWi5DLwAssQCQ1rfE48lgnKpgAFmy3WdkiqJi50I-vYYUhiQmCzrfP599ANwgtEII0TGK7MekVRgvAOGGMk0YYKTXTCMM5xIzvAAHISwQghJSek-GFBEcSoEHoL7PH8gcO1d7Vob4MJ3S-htKEOrG2Nh2UAXWuuC9sbVGs430DavcVQ2Szi5zKcE2o91fBBK1xyBvUJXwR5vz0Pwcn31nN8ks8fpbT6ZJYZyihPMuCBULijLCOGp1oJjTguepdySOdaYISszUTBdCEGZFCReqDZSMFFww-ghOO9z49pvnQ2tqstgbFXpxrouKIIJIohliER69oeuXOebuF1UGY3fZCyN6qJXxrsQvC3U2pe19huFkfpqWMWG1XfD0Z5uE7t5bRe_8qfSCMY9eC8ru_k_Sd3lT33kJ_UegXg</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Tsai, Hsiao‐Chi</creator><creator>Chang, An‐Chen</creator><creator>Tsai, Chun‐Hao</creator><creator>Huang, Yuan‐Li</creator><creator>Gan, Lijun</creator><creator>Chen, Chi‐Kuan</creator><creator>Liu, Shih‐Chia</creator><creator>Huang, Te‐Yang</creator><creator>Fong, Yi‐Chin</creator><creator>Tang, Chih‐Hsin</creator><general>Wiley Subscription Services, Inc</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>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3405-8863</orcidid><orcidid>https://orcid.org/0000-0002-7113-8352</orcidid></search><sort><creationdate>201906</creationdate><title>CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression</title><author>Tsai, Hsiao‐Chi ; Chang, An‐Chen ; Tsai, Chun‐Hao ; Huang, Yuan‐Li ; Gan, Lijun ; Chen, Chi‐Kuan ; Liu, Shih‐Chia ; Huang, Te‐Yang ; Fong, Yi‐Chin ; Tang, Chih‐Hsin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-1456239d3482257aa65153f5875e2b1a140e986f4af663496286f3ac9646f5c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>ABCG2</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics</topic><topic>Base Sequence</topic><topic>Binding</topic><topic>Biocompatibility</topic><topic>Bone cancer</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>CCN2</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - genetics</topic><topic>Chemoresistance</topic><topic>chemotherapeutic resistance</topic><topic>Connective tissue growth factor</topic><topic>Connective Tissue Growth Factor - metabolism</topic><topic>Doxorubicin</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Integrin alpha6beta1 - metabolism</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Models, Biological</topic><topic>Neoplasm Proteins - genetics</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma - genetics</topic><topic>Proteins</topic><topic>Sarcoma</topic><topic>Signal Transduction</topic><topic>Survival</topic><topic>Xenobiotics</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Hsiao‐Chi</creatorcontrib><creatorcontrib>Chang, An‐Chen</creatorcontrib><creatorcontrib>Tsai, Chun‐Hao</creatorcontrib><creatorcontrib>Huang, Yuan‐Li</creatorcontrib><creatorcontrib>Gan, Lijun</creatorcontrib><creatorcontrib>Chen, Chi‐Kuan</creatorcontrib><creatorcontrib>Liu, Shih‐Chia</creatorcontrib><creatorcontrib>Huang, Te‐Yang</creatorcontrib><creatorcontrib>Fong, Yi‐Chin</creatorcontrib><creatorcontrib>Tang, Chih‐Hsin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Hsiao‐Chi</au><au>Chang, An‐Chen</au><au>Tsai, Chun‐Hao</au><au>Huang, Yuan‐Li</au><au>Gan, Lijun</au><au>Chen, Chi‐Kuan</au><au>Liu, Shih‐Chia</au><au>Huang, Te‐Yang</au><au>Fong, Yi‐Chin</au><au>Tang, Chih‐Hsin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2019-06</date><risdate>2019</risdate><volume>234</volume><issue>6</issue><spage>9297</spage><epage>9307</epage><pages>9297-9307</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.
Chemoresistance is an important problem in osteosarcoma. CCN2 promotes drug resistance in osteosarcoma. CCN2 increases ABCG2 protein expression and activation in osteosarcoma</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30317661</pmid><doi>10.1002/jcp.27611</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3405-8863</orcidid><orcidid>https://orcid.org/0000-0002-7113-8352</orcidid></addata></record> |
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| subjects | ABCG2 Animals ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics Base Sequence Binding Biocompatibility Bone cancer Breast cancer Cancer CCN2 Cell Line, Tumor Cell Survival - genetics Chemoresistance chemotherapeutic resistance Connective tissue growth factor Connective Tissue Growth Factor - metabolism Doxorubicin Drug resistance Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic Humans Integrin alpha6beta1 - metabolism Mice MicroRNAs - genetics MicroRNAs - metabolism Models, Biological Neoplasm Proteins - genetics Osteosarcoma Osteosarcoma - genetics Proteins Sarcoma Signal Transduction Survival Xenobiotics Xenografts Xenotransplantation |
| title | CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression |
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