Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework
Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D) in-vitro culture models of tumorigenesis are inadequate to replicate the complexity of in-vivo microenviron...
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| Veröffentlicht in: | Scientific reports 2019-06, Vol.9 (1), p.8997-11, Article 8997 |
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| creator | Pal, Mintu Chen, Huizhi Lee, Bae Hoon Lee, Justin Yin Hao Yip, Yun Sheng Tan, Nguan Soon Tan, Lay Poh |
| description | Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D)
in-vitro
culture models of tumorigenesis are inadequate to replicate the complexity of
in-vivo
microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis. |
| doi_str_mv | 10.1038/s41598-019-45384-9 |
| format | Article |
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in-vitro
culture models of tumorigenesis are inadequate to replicate the complexity of
in-vivo
microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-45384-9</identifier><identifier>PMID: 31222037</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14 ; 14/19 ; 38 ; 38/77 ; 631/67/70 ; 639/301/54/2295 ; Biocompatible Materials ; Biomarkers ; Biomedical Engineering - methods ; Breast cancer ; Cancer ; Cell culture ; Cell Culture Techniques ; Cell Line, Tumor ; Cell proliferation ; Chemoresistance ; E-cadherin ; Epithelial-Mesenchymal Transition ; Fabrication ; Fibers ; Fluorescent Antibody Technique ; Gastric cancer ; Gene regulation ; Humanities and Social Sciences ; Humans ; Hydrogels ; Mesenchyme ; Metastases ; Metastasis ; multidisciplinary ; Neoplasms - pathology ; Phenotypes ; Science ; Science (multidisciplinary) ; Spheroids ; Spheroids, Cellular ; Stem cells ; Tissue Scaffolds ; Transcription factors ; Tumorigenesis ; Tumors</subject><ispartof>Scientific reports, 2019-06, Vol.9 (1), p.8997-11, Article 8997</ispartof><rights>The Author(s) 2019</rights><rights>2019. 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-1ac93fa518134f9a3a22578d62bcd6bb380ea285a3d1981ca9fbf466188719193</citedby><cites>FETCH-LOGICAL-c474t-1ac93fa518134f9a3a22578d62bcd6bb380ea285a3d1981ca9fbf466188719193</cites><orcidid>0000-0003-0136-7341 ; 0000-0002-7222-0008</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/PMC6586872/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586872/$$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/31222037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pal, Mintu</creatorcontrib><creatorcontrib>Chen, Huizhi</creatorcontrib><creatorcontrib>Lee, Bae Hoon</creatorcontrib><creatorcontrib>Lee, Justin Yin Hao</creatorcontrib><creatorcontrib>Yip, Yun Sheng</creatorcontrib><creatorcontrib>Tan, Nguan Soon</creatorcontrib><creatorcontrib>Tan, Lay Poh</creatorcontrib><title>Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D)
in-vitro
culture models of tumorigenesis are inadequate to replicate the complexity of
in-vivo
microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.</description><subject>14</subject><subject>14/19</subject><subject>38</subject><subject>38/77</subject><subject>631/67/70</subject><subject>639/301/54/2295</subject><subject>Biocompatible Materials</subject><subject>Biomarkers</subject><subject>Biomedical Engineering - methods</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cell Culture Techniques</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Chemoresistance</subject><subject>E-cadherin</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Fabrication</subject><subject>Fibers</subject><subject>Fluorescent Antibody Technique</subject><subject>Gastric cancer</subject><subject>Gene regulation</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Mesenchyme</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>multidisciplinary</subject><subject>Neoplasms - 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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>Pal, Mintu</au><au>Chen, Huizhi</au><au>Lee, Bae Hoon</au><au>Lee, Justin Yin Hao</au><au>Yip, Yun Sheng</au><au>Tan, Nguan Soon</au><au>Tan, Lay Poh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-06-20</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>8997</spage><epage>11</epage><pages>8997-11</pages><artnum>8997</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Cancer cells undergoing epithelial-mesenchymal transition (EMT) acquire stem cell-like phenotype associated with malignant behaviour, chemoresistance, and relapse. Current two-dimensional (2D)
in-vitro
culture models of tumorigenesis are inadequate to replicate the complexity of
in-vivo
microenvironment. Therefore, the generation of functional three-dimensional (3D) constructs is a fundamental prerequisite to form multi-cellular tumour spheroids for studying basic pathological mechanisms. In this study, we focused on two major points (i) designing and fabrication of 3D hybrid scaffolds comprising electrospun fibers with cancer cells embedded within hydrogels, and (ii) determining the potential roles of 3D hybrid scaffolds associated with EMT in cancer progression and metastasis. Our findings revealed that 3D hybrid scaffold enhances cell proliferation and induces cancer cells to undergo EMT, as demonstrated by significant up-regulation of EMT associated transcriptional factors including Snail1, Zeb1, and Twist2; and mesenchymal markers whereas epithelial marker, E-Cadherin was downregulated. Remarkably, this induction is independent of cancer cell-type as similar results were obtained for breast cancer cells, MDA-MB-231 and gastric cancer cells, MKN74. Moreover, the hybrid scaffolds enrich aggressive cancer cells with stem cell properties. We showed that our 3D scaffolds could trigger EMT of cancer cells which could provide a useful model for studying anticancer therapeutics against metastasis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31222037</pmid><doi>10.1038/s41598-019-45384-9</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0136-7341</orcidid><orcidid>https://orcid.org/0000-0002-7222-0008</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Nature Open Access; MEDLINE; 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 | 14 14/19 38 38/77 631/67/70 639/301/54/2295 Biocompatible Materials Biomarkers Biomedical Engineering - methods Breast cancer Cancer Cell culture Cell Culture Techniques Cell Line, Tumor Cell proliferation Chemoresistance E-cadherin Epithelial-Mesenchymal Transition Fabrication Fibers Fluorescent Antibody Technique Gastric cancer Gene regulation Humanities and Social Sciences Humans Hydrogels Mesenchyme Metastases Metastasis multidisciplinary Neoplasms - pathology Phenotypes Science Science (multidisciplinary) Spheroids Spheroids, Cellular Stem cells Tissue Scaffolds Transcription factors Tumorigenesis Tumors |
| title | Epithelial-mesenchymal transition of cancer cells using bioengineered hybrid scaffold composed of hydrogel/3D-fibrous framework |
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