Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes
Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tu...
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| creator | Ohta, Naomi Ishiguro, Susumu Kawabata, Atsushi Uppalapati, Deepthi Pyle, Marla Troyer, Deryl De, Supriyo Zhang, Yongqing Becker, Kevin G Tamura, Masaaki |
| description | Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression. |
| doi_str_mv | 10.1371/journal.pone.0123756 |
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Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0123756</identifier><identifier>PMID: 25942583</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis - physiology ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - physiopathology ; Care and treatment ; Cell Line, Tumor ; Cell Proliferation - physiology ; Cells, Cultured ; Cluster Analysis ; Conditioning ; DNA microarrays ; Female ; Follistatin ; Follistatin - metabolism ; Follistatin gene ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Genomics ; Growth ; Health aspects ; Human performance ; Humans ; Kinases ; Lung cancer ; Lung carcinoma ; Membrane Proteins - metabolism ; Mesenchymal stem cells ; Mesenchymal Stem Cells - physiology ; Mesenchyme ; Metastases ; Oligonucleotide Array Sequence Analysis ; Overexpression ; Perilipin-2 ; Rats ; Real-Time Polymerase Chain Reaction ; Rodents ; Stability ; Stem cell transplantation ; Stem cells ; Tumor suppressor genes ; Tumors ; Umbilical cord ; Veterinary colleges</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0123756-e0123756</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”) Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e474cff34312896678ae4155788fe50a69a754573ce16fa535fdb4f23caa89143</citedby><cites>FETCH-LOGICAL-c692t-e474cff34312896678ae4155788fe50a69a754573ce16fa535fdb4f23caa89143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420498/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420498/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25942583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Samant, Rajeev</contributor><creatorcontrib>Ohta, Naomi</creatorcontrib><creatorcontrib>Ishiguro, Susumu</creatorcontrib><creatorcontrib>Kawabata, Atsushi</creatorcontrib><creatorcontrib>Uppalapati, Deepthi</creatorcontrib><creatorcontrib>Pyle, Marla</creatorcontrib><creatorcontrib>Troyer, Deryl</creatorcontrib><creatorcontrib>De, Supriyo</creatorcontrib><creatorcontrib>Zhang, Yongqing</creatorcontrib><creatorcontrib>Becker, Kevin G</creatorcontrib><creatorcontrib>Tamura, Masaaki</creatorcontrib><title>Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - physiopathology</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - physiology</subject><subject>Cells, Cultured</subject><subject>Cluster Analysis</subject><subject>Conditioning</subject><subject>DNA microarrays</subject><subject>Female</subject><subject>Follistatin</subject><subject>Follistatin - metabolism</subject><subject>Follistatin gene</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Growth</subject><subject>Health aspects</subject><subject>Human performance</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Membrane Proteins - metabolism</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Overexpression</subject><subject>Perilipin-2</subject><subject>Rats</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Stability</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Umbilical cord</subject><subject>Veterinary colleges</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBYQkJw2CX-yscFqaqArlSpEl9Xa-JMslkl8dZ2oHvir-N009UG9YB8iDV-3teZ8UwUvaTxkvKUftiYwfbQLremx2VMGU9l8ig6pTlni4TF_PHR_iR65twmjiXPkuRpdMJkLpjM-Gn053LooCdDVzRto6El2tiSdOBtc0s6dNjr9a4LceexIxrb1hE3bLcWnSN-jaS25rdfE1ORwiI4TzT0Gi0pdgRv77DG9OOxHzpjD9qwrbFH9zx6UkHr8MX0PYt-fP70_eJycXX9ZXVxfrXQSc78AkUqdFVxwSnL8iRJM0BBpUyzrEIZQ5JDKoVMuUaaVCC5rMpCVIxrgCyngp9Fr_e-29Y4NdXOKRqcUpkmjAVitSdKAxu1tU0HdqcMNOouYGytwPpGt6hYsC6AU1nQUpQAOZYU8yLEYpHqSgavj9NtQ9FhqbH3FtqZ6fykb9aqNr-UECwWeRYM3k0G1twM6LzqGjdWH3o0w_jfWUyzhCVjZm_-QR_ObqJqCAk0fWXCvXo0VeeCx6FTQm8EavkAFVaJXaNDo1VNiM8E72eCwHi89TUMzqnVt6__z17_nLNvj9g1QuvXzrSDD83k5qDYg9oa5yxWhyLTWI1zcl8NNc6JmuYkyF4dP9BBdD8Y_C_iqxAu</recordid><startdate>20150505</startdate><enddate>20150505</enddate><creator>Ohta, Naomi</creator><creator>Ishiguro, Susumu</creator><creator>Kawabata, Atsushi</creator><creator>Uppalapati, Deepthi</creator><creator>Pyle, Marla</creator><creator>Troyer, Deryl</creator><creator>De, Supriyo</creator><creator>Zhang, Yongqing</creator><creator>Becker, Kevin G</creator><creator>Tamura, Masaaki</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150505</creationdate><title>Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes</title><author>Ohta, Naomi ; Ishiguro, Susumu ; Kawabata, Atsushi ; Uppalapati, Deepthi ; Pyle, Marla ; Troyer, Deryl ; De, Supriyo ; Zhang, Yongqing ; Becker, Kevin G ; Tamura, Masaaki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e474cff34312896678ae4155788fe50a69a754573ce16fa535fdb4f23caa89143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Apoptosis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohta, Naomi</au><au>Ishiguro, Susumu</au><au>Kawabata, Atsushi</au><au>Uppalapati, Deepthi</au><au>Pyle, Marla</au><au>Troyer, Deryl</au><au>De, Supriyo</au><au>Zhang, Yongqing</au><au>Becker, Kevin G</au><au>Tamura, Masaaki</au><au>Samant, Rajeev</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-05</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0123756</spage><epage>e0123756</epage><pages>e0123756-e0123756</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25942583</pmid><doi>10.1371/journal.pone.0123756</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0123756-e0123756 |
| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Apoptosis - physiology Breast cancer Breast carcinoma Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - physiopathology Care and treatment Cell Line, Tumor Cell Proliferation - physiology Cells, Cultured Cluster Analysis Conditioning DNA microarrays Female Follistatin Follistatin - metabolism Follistatin gene Gene expression Gene Expression Regulation, Neoplastic Genes Genetic aspects Genomics Growth Health aspects Human performance Humans Kinases Lung cancer Lung carcinoma Membrane Proteins - metabolism Mesenchymal stem cells Mesenchymal Stem Cells - physiology Mesenchyme Metastases Oligonucleotide Array Sequence Analysis Overexpression Perilipin-2 Rats Real-Time Polymerase Chain Reaction Rodents Stability Stem cell transplantation Stem cells Tumor suppressor genes Tumors Umbilical cord Veterinary colleges |
| title | Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T22%3A48%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20umbilical%20cord%20matrix%20mesenchymal%20stem%20cells%20suppress%20the%20growth%20of%20breast%20cancer%20by%20expression%20of%20tumor%20suppressor%20genes&rft.jtitle=PloS%20one&rft.au=Ohta,%20Naomi&rft.date=2015-05-05&rft.volume=10&rft.issue=5&rft.spage=e0123756&rft.epage=e0123756&rft.pages=e0123756-e0123756&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0123756&rft_dat=%3Cgale_plos_%3EA430193538%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1678757622&rft_id=info:pmid/25942583&rft_galeid=A430193538&rft_doaj_id=oai_doaj_org_article_2b4fba315b1d4daa9ed1e9bfba047cf5&rfr_iscdi=true |