Enhanced ASGR2 by microplastic exposure leads to resistance to therapy in gastric cancer
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Hyeongi | - |
dc.contributor.author | Zaheer, Javeria | - |
dc.contributor.author | Choi, Eui-Ju | - |
dc.contributor.author | Kim, Jin Su | - |
dc.date.accessioned | 2022-06-12T15:40:20Z | - |
dc.date.available | 2022-06-12T15:40:20Z | - |
dc.date.created | 2022-06-09 | - |
dc.date.issued | 2022 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/142150 | - |
dc.description.abstract | Background: Microplastics (MPs) are a new global environmental threat. Previously, we showed the biodistribution of MPs using [Cu-64] polystyrene (PS) and PET in mice. Here, we aimed to identify whether PS exposure has malignant effects on the stomach and induces resistance to therapy. Methods: BALB/c nude mice were fed 1.72 x 10(4) particles/mL of MP. We investigated PS accumulation in the stomach using radioisotope-labeled and fluorescent-conjugated PS. Further, we evaluated whether PS exposure induced cancer stemness and multidrug resistance, and whether it affected tumor development, tumor growth, and survival rate in vivo using a 4-week PS-exposed NCI-N87 mouse model. Using RNA-Seq analysis, we analyzed whether PS exposure induced gene expression changes in gastric tissues of mice. Results: PET imaging results showed that a single dose of [Cu-64]-PS remained for 24 h in the mice stomach. The 4-week daily repetitive dose of fluorescent conjugated PS was deposited in the gastric tissues of mice. When PS was exposed, a 2.9-fold increase in migration rate was observed for NCI-N87 cells. Immunocytochemistry results showed decreased E-cadherin and increased N-cadherin expression, and flow cytometry, qPCR, and western blot analysis indicated a 1.9-fold increase in N-cadherin expression after PS exposure. Further, PS-induced multidrug resistance to bortezomib, paclitaxel, gefitinib, lapatinib, and trastuzumab was observed in the NCI-N87 mouse model due to upregulated CD44 expression. RNA-seq results identified increased asialoglycoprotein receptor 2 (ASGR2) expression after PS exposure, and ASGR2 knockdown decreased cell proliferation, migration, invasion, and drug resistance. Conclusion: We demonstrated that ASGR2 enhanced cancer hallmarks on PS exposure and induced resistance to chemo- and monoclonal antibody-therapy. Our preclinical findings may provide an incentive for further epidemiological studies on the role of MP exposure and its association with gastric cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | IVYSPRING INT PUBL | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | READ ALIGNMENT | - |
dc.subject | CD44 | - |
dc.subject | ISOFORM | - |
dc.subject | CELLS | - |
dc.subject | TUMOR | - |
dc.subject | STRINGTIE | - |
dc.subject | STRESS | - |
dc.subject | BREAST | - |
dc.subject | LEVEL | - |
dc.title | Enhanced ASGR2 by microplastic exposure leads to resistance to therapy in gastric cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Choi, Eui-Ju | - |
dc.identifier.doi | 10.7150/thno.73226 | - |
dc.identifier.scopusid | 2-s2.0-85128709923 | - |
dc.identifier.wosid | 000786579800012 | - |
dc.identifier.bibliographicCitation | THERANOSTICS, v.12, no.7, pp.3217 - 3236 | - |
dc.relation.isPartOf | THERANOSTICS | - |
dc.citation.title | THERANOSTICS | - |
dc.citation.volume | 12 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 3217 | - |
dc.citation.endPage | 3236 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | READ ALIGNMENT | - |
dc.subject.keywordPlus | CD44 | - |
dc.subject.keywordPlus | ISOFORM | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | TUMOR | - |
dc.subject.keywordPlus | STRINGTIE | - |
dc.subject.keywordPlus | STRESS | - |
dc.subject.keywordPlus | BREAST | - |
dc.subject.keywordPlus | LEVEL | - |
dc.subject.keywordAuthor | Microplastics | - |
dc.subject.keywordAuthor | gastric cancer | - |
dc.subject.keywordAuthor | cancer hallmarks | - |
dc.subject.keywordAuthor | polystyrene | - |
dc.subject.keywordAuthor | ASGR2 | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea+82-2-3290-2963
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.