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Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer

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dc.contributor.authorHam, In-Hye-
dc.contributor.authorOh, Hye Jeong-
dc.contributor.authorJin, Hyejin-
dc.contributor.authorBae, Cheong A.-
dc.contributor.authorJeon, Sang-Min-
dc.contributor.authorChoi, Kyeong Sook-
dc.contributor.authorSon, Sang-Yong-
dc.contributor.authorHan, Sang-Uk-
dc.contributor.authorBrekken, Rolf A.-
dc.contributor.authorLee, Dakeun-
dc.contributor.authorHur, Hoon-
dc.date.accessioned2024-05-02T06:01:12Z-
dc.date.available2024-05-02T06:01:12Z-
dc.date.created2023-04-15-
dc.date.created2023-04-15-
dc.date.created2023-04-15-
dc.date.issued2019-03-
dc.identifier.citationMolecular Cancer, Vol.18 No.1, p. 68-
dc.identifier.issn1476-4598-
dc.identifier.urihttps://hdl.handle.net/10371/200535-
dc.description.abstractBackgroundAlthough the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC.MethodsTo identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues.ResultsSecretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy.ConclusionsOur data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.-
dc.language영어-
dc.publisherBioMed Central-
dc.titleTargeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer-
dc.typeArticle-
dc.identifier.doi10.1186/s12943-019-0972-8-
dc.citation.journaltitleMolecular Cancer-
dc.identifier.wosid000462941900013-
dc.identifier.scopusid2-s2.0-85063750322-
dc.citation.number1-
dc.citation.startpage68-
dc.citation.volume18-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorJeon, Sang-Min-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.subject.keywordPlusANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY-
dc.subject.keywordPlusHUMAN BREAST-
dc.subject.keywordPlusAGGRESSIVE PHENOTYPE-
dc.subject.keywordPlusDRUG-RESISTANCE-
dc.subject.keywordPlusSUPPORTIVE CARE-
dc.subject.keywordPlusFIBROBLASTS-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusIL-6-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusPATHWAY-
dc.subject.keywordAuthorGastric cancer-
dc.subject.keywordAuthorCancer-associated fibroblasts-
dc.subject.keywordAuthorTumor microenvironment-
dc.subject.keywordAuthorChemo-resistance-
dc.subject.keywordAuthorInterleukin-6-
dc.subject.keywordAuthorTocilizumab-
dc.subject.keywordAuthorJak1-STAT3-
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  • College of Pharmacy
  • Department of Pharmacy
Research Area Cancer Origin, Metabolism, Toxicology

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