A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments
Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a “tumor section”-like culture by incorporating...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2017-11, Vol.7 (1), p.15233-12, Article 15233 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 12 |
|---|---|
| container_issue | 1 |
| container_start_page | 15233 |
| container_title | Scientific reports |
| container_volume | 7 |
| creator | Ando, Yuta Ta, Hoang P. Yen, Daniel P. Lee, Sang-Sin Raola, Sneha Shen, Keyue |
| description | Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a “tumor section”-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement. We also demonstrated spatially-resolved hypoxic signaling in cancer cells through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological processes, and discovery of new therapeutics. |
| doi_str_mv | 10.1038/s41598-017-15583-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5680268</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1963270587</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-a89af3c7015157ed1b08cb47677cdee40baf1e6a38241c4192a020ee154d07d83</originalsourceid><addsrcrecordid>eNp1kU1LxDAQhoMoKuof8CAFL16q-WzSiyCyfoCiiJ5DNp2ukbZZk3bRf2_WqqyCuSTDPPPOTF6E9gk-Jpipk8iJKFWOicyJEIrlbA1tU8xFThml6yvvLbQX4wtOR9CSk3ITbdGSUEZKuY0mZ9mts8FXsHAWsvvG9LUPbfYA1sxdP6TYdbPs6n3u35zNHofWh7ECuoULvmuh6-Mu2qhNE2Hv695BTxeTx_Or_Obu8vr87Ca3XPI-N6o0NbMSE0GEhIpMsbJTLgspbQXA8dTUBArDFOXEplGpwRQDEMErLCvFdtDpqDsfpi1UNvUOptHz4FoT3rU3Tv_OdO5Zz_xCi0JhWiwFjr4Egn8dIPa6ddFC05gO_BA1KQtGJRZKJvTwD_rih9Cl9ZYUpUKJAieKjlT6kRgD1D_DEKyXRunRKJ2M0p9GaZaKDlbX-Cn5tiUBbARiSnUzCCu9_5f9AG9znrY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1962258560</pqid></control><display><type>article</type><title>A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Ando, Yuta ; Ta, Hoang P. ; Yen, Daniel P. ; Lee, Sang-Sin ; Raola, Sneha ; Shen, Keyue</creator><creatorcontrib>Ando, Yuta ; Ta, Hoang P. ; Yen, Daniel P. ; Lee, Sang-Sin ; Raola, Sneha ; Shen, Keyue</creatorcontrib><description>Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a “tumor section”-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement. We also demonstrated spatially-resolved hypoxic signaling in cancer cells through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological processes, and discovery of new therapeutics.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-15583-3</identifier><identifier>PMID: 29123197</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/107 ; 14/63 ; 631/61 ; 631/67 ; 631/67/327 ; 639/166/985 ; 9/10 ; Cancer ; Cell culture ; Cytological Techniques - instrumentation ; Cytological Techniques - methods ; Gene expression ; Gene Expression Profiling ; Humanities and Social Sciences ; Humans ; Hypoxia ; Immunohistochemistry ; Mathematical models ; MCF-7 Cells ; Microenvironments ; Microfluidics ; multidisciplinary ; Neoplasms - pathology ; Oxygen ; Oxygen - analysis ; Science ; Science (multidisciplinary) ; Solid tumors ; Tumor Microenvironment ; Tumors</subject><ispartof>Scientific reports, 2017-11, Vol.7 (1), p.15233-12, Article 15233</ispartof><rights>The Author(s) 2017</rights><rights>2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (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-c474t-a89af3c7015157ed1b08cb47677cdee40baf1e6a38241c4192a020ee154d07d83</citedby><cites>FETCH-LOGICAL-c474t-a89af3c7015157ed1b08cb47677cdee40baf1e6a38241c4192a020ee154d07d83</cites><orcidid>0000-0001-9605-1635</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680268/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680268/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29123197$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ando, Yuta</creatorcontrib><creatorcontrib>Ta, Hoang P.</creatorcontrib><creatorcontrib>Yen, Daniel P.</creatorcontrib><creatorcontrib>Lee, Sang-Sin</creatorcontrib><creatorcontrib>Raola, Sneha</creatorcontrib><creatorcontrib>Shen, Keyue</creatorcontrib><title>A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a “tumor section”-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement. We also demonstrated spatially-resolved hypoxic signaling in cancer cells through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological processes, and discovery of new therapeutics.</description><subject>13/100</subject><subject>13/107</subject><subject>14/63</subject><subject>631/61</subject><subject>631/67</subject><subject>631/67/327</subject><subject>639/166/985</subject><subject>9/10</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cytological Techniques - instrumentation</subject><subject>Cytological Techniques - methods</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Mathematical models</subject><subject>MCF-7 Cells</subject><subject>Microenvironments</subject><subject>Microfluidics</subject><subject>multidisciplinary</subject><subject>Neoplasms - pathology</subject><subject>Oxygen</subject><subject>Oxygen - analysis</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Solid tumors</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1LxDAQhoMoKuof8CAFL16q-WzSiyCyfoCiiJ5DNp2ukbZZk3bRf2_WqqyCuSTDPPPOTF6E9gk-Jpipk8iJKFWOicyJEIrlbA1tU8xFThml6yvvLbQX4wtOR9CSk3ITbdGSUEZKuY0mZ9mts8FXsHAWsvvG9LUPbfYA1sxdP6TYdbPs6n3u35zNHofWh7ECuoULvmuh6-Mu2qhNE2Hv695BTxeTx_Or_Obu8vr87Ca3XPI-N6o0NbMSE0GEhIpMsbJTLgspbQXA8dTUBArDFOXEplGpwRQDEMErLCvFdtDpqDsfpi1UNvUOptHz4FoT3rU3Tv_OdO5Zz_xCi0JhWiwFjr4Egn8dIPa6ddFC05gO_BA1KQtGJRZKJvTwD_rih9Cl9ZYUpUKJAieKjlT6kRgD1D_DEKyXRunRKJ2M0p9GaZaKDlbX-Cn5tiUBbARiSnUzCCu9_5f9AG9znrY</recordid><startdate>20171109</startdate><enddate>20171109</enddate><creator>Ando, Yuta</creator><creator>Ta, Hoang P.</creator><creator>Yen, Daniel P.</creator><creator>Lee, Sang-Sin</creator><creator>Raola, Sneha</creator><creator>Shen, Keyue</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9605-1635</orcidid></search><sort><creationdate>20171109</creationdate><title>A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments</title><author>Ando, Yuta ; Ta, Hoang P. ; Yen, Daniel P. ; Lee, Sang-Sin ; Raola, Sneha ; Shen, Keyue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-a89af3c7015157ed1b08cb47677cdee40baf1e6a38241c4192a020ee154d07d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/100</topic><topic>13/107</topic><topic>14/63</topic><topic>631/61</topic><topic>631/67</topic><topic>631/67/327</topic><topic>639/166/985</topic><topic>9/10</topic><topic>Cancer</topic><topic>Cell culture</topic><topic>Cytological Techniques - instrumentation</topic><topic>Cytological Techniques - methods</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Immunohistochemistry</topic><topic>Mathematical models</topic><topic>MCF-7 Cells</topic><topic>Microenvironments</topic><topic>Microfluidics</topic><topic>multidisciplinary</topic><topic>Neoplasms - pathology</topic><topic>Oxygen</topic><topic>Oxygen - analysis</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Solid tumors</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ando, Yuta</creatorcontrib><creatorcontrib>Ta, Hoang P.</creatorcontrib><creatorcontrib>Yen, Daniel P.</creatorcontrib><creatorcontrib>Lee, Sang-Sin</creatorcontrib><creatorcontrib>Raola, Sneha</creatorcontrib><creatorcontrib>Shen, Keyue</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ando, Yuta</au><au>Ta, Hoang P.</au><au>Yen, Daniel P.</au><au>Lee, Sang-Sin</au><au>Raola, Sneha</au><au>Shen, Keyue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-11-09</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>15233</spage><epage>12</epage><pages>15233-12</pages><artnum>15233</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Hypoxia plays a central role in cancer progression and resistance to therapy. We have engineered a microdevice platform to recapitulate the intratumor oxygen gradients that drive the heterogeneous hypoxic landscapes in solid tumors. Our design features a “tumor section”-like culture by incorporating a cell layer between two diffusion barriers, where an oxygen gradient is established by cellular metabolism and physical constraints. We confirmed the oxygen gradient by numerical simulation and imaging-based oxygen sensor measurement. We also demonstrated spatially-resolved hypoxic signaling in cancer cells through immunostaining, gene expression assay, and hypoxia-targeted drug treatment. Our platform can accurately generate and control oxygen gradients, eliminates complex microfluidic handling, allows for incorporation of additional tumor components, and is compatible with high-content imaging and high-throughput applications. It is well suited for understanding hypoxia-mediated mechanisms in cancer disease and other biological processes, and discovery of new therapeutics.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29123197</pmid><doi>10.1038/s41598-017-15583-3</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9605-1635</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2017-11, Vol.7 (1), p.15233-12, Article 15233 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5680268 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 13/100 13/107 14/63 631/61 631/67 631/67/327 639/166/985 9/10 Cancer Cell culture Cytological Techniques - instrumentation Cytological Techniques - methods Gene expression Gene Expression Profiling Humanities and Social Sciences Humans Hypoxia Immunohistochemistry Mathematical models MCF-7 Cells Microenvironments Microfluidics multidisciplinary Neoplasms - pathology Oxygen Oxygen - analysis Science Science (multidisciplinary) Solid tumors Tumor Microenvironment Tumors |
| title | A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T06%3A47%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Microdevice%20Platform%20Recapitulating%20Hypoxic%20Tumor%20Microenvironments&rft.jtitle=Scientific%20reports&rft.au=Ando,%20Yuta&rft.date=2017-11-09&rft.volume=7&rft.issue=1&rft.spage=15233&rft.epage=12&rft.pages=15233-12&rft.artnum=15233&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-017-15583-3&rft_dat=%3Cproquest_pubme%3E1963270587%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1962258560&rft_id=info:pmid/29123197&rfr_iscdi=true |