Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a novel 3D model for investigation of stroma-mediated cell motility and drug resistance
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Hyun | - |
dc.contributor.author | Kim, Seul-Ki | - |
dc.contributor.author | Khawar, Lftikhar Ali | - |
dc.contributor.author | Jeong, Su-Yeong | - |
dc.contributor.author | Chung, Seok | - |
dc.contributor.author | Kuh, Hyo-Jeong | - |
dc.date.accessioned | 2021-09-02T16:11:37Z | - |
dc.date.available | 2021-09-02T16:11:37Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-01-12 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/77985 | - |
dc.description.abstract | Background: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithefial-mesenchymal transition and chemoresistance. Methods: A 7-channel microchannel plate was prepared using poly-dimethylsiloxane (PDMS) via soft lithography. PANC-1, a human pancreatic cancer cell line, and PSCs, each within a designated channel of the microchannel plate, were cultured embedded in type I collagen. Expression of EMT-related markers and factors was analyzed using immunofluorescent staining or Proteome analysis. Changes in viability following exposure to gemcitabine and paclitaxel were measured using Live/Dead assay. Results: PANC-1 cells formed 3D tumor spheroids within 5 days and the number of spheroids increased when co-cultured with PSCs. Culture conditions were optimized for PANC-1 cells and PSCs, and their appropriate interaction was confirmed by reciprocal activation shown as increased cell motility. PSCs under co-culture showed an increased expression of alpha-SMA. Expression of EMT-related markers, such as vimentin and TGF-beta, was higher in co-cultured PANC-1 spheroids compared to that in mono-cultured spheroids; as was the expression of many other EMT-related factors including TIMP1 and IL-8. Following gemcitabine exposure, no significant changes in survival were observed. When paclitaxel was combined with gemcitabine, a growth inhibitory advantage was prominent in tumor spheroids, which was accompanied by significant cytotoxicity in PSCs. Conclusions: We demonstrated that cancer cells grown as tumor spheroids in a 3D collagen matrix and PSCs co-cultured in sub-millimeter proximity participate in mutual interactions that induce EMT and drug resistance in a microchannel plate. Microfluidic co-culture of pancreatic tumor spheroids with PSCs may serve as a useful mode ! for studying EMT and drug resistance in a clinically relevant manner. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BIOMED CENTRAL LTD | - |
dc.subject | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject | DUCTAL ADENOCARCINOMA | - |
dc.subject | CANCER CELLS | - |
dc.subject | NAB-PACLITAXEL | - |
dc.subject | COLORECTAL-CANCER | - |
dc.subject | IN-VITRO | - |
dc.subject | MICROENVIRONMENT | - |
dc.subject | CULTURE | - |
dc.subject | PROGRESSION | - |
dc.subject | FIBROBLASTS | - |
dc.title | Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a novel 3D model for investigation of stroma-mediated cell motility and drug resistance | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Chung, Seok | - |
dc.identifier.doi | 10.1186/s13046-017-0654-6 | - |
dc.identifier.scopusid | 2-s2.0-85040455387 | - |
dc.identifier.wosid | 000419983500001 | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, v.37 | - |
dc.relation.isPartOf | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | - |
dc.citation.title | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | - |
dc.citation.volume | 37 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | DUCTAL ADENOCARCINOMA | - |
dc.subject.keywordPlus | CANCER CELLS | - |
dc.subject.keywordPlus | NAB-PACLITAXEL | - |
dc.subject.keywordPlus | COLORECTAL-CANCER | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | MICROENVIRONMENT | - |
dc.subject.keywordPlus | CULTURE | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | FIBROBLASTS | - |
dc.subject.keywordAuthor | MicroChannel plate | - |
dc.subject.keywordAuthor | EMT | - |
dc.subject.keywordAuthor | Pancreatic cancer | - |
dc.subject.keywordAuthor | Cancer-Stroma co-culture | - |
dc.subject.keywordAuthor | Tumor microenvironment | - |
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