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Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer
DC Field | Value | Language |
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dc.contributor.author | Ham, In-Hye | - |
dc.contributor.author | Oh, Hye Jeong | - |
dc.contributor.author | Jin, Hyejin | - |
dc.contributor.author | Bae, Cheong A. | - |
dc.contributor.author | Jeon, Sang-Min | - |
dc.contributor.author | Choi, Kyeong Sook | - |
dc.contributor.author | Son, Sang-Yong | - |
dc.contributor.author | Han, Sang-Uk | - |
dc.contributor.author | Brekken, Rolf A. | - |
dc.contributor.author | Lee, Dakeun | - |
dc.contributor.author | Hur, Hoon | - |
dc.date.accessioned | 2024-05-02T06:01:12Z | - |
dc.date.available | 2024-05-02T06:01:12Z | - |
dc.date.created | 2023-04-15 | - |
dc.date.created | 2023-04-15 | - |
dc.date.created | 2023-04-15 | - |
dc.date.issued | 2019-03 | - |
dc.identifier.citation | Molecular Cancer, Vol.18 No.1, p. 68 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://hdl.handle.net/10371/200535 | - |
dc.description.abstract | BackgroundAlthough 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.language | 영어 | - |
dc.publisher | BioMed Central | - |
dc.title | Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer | - |
dc.type | Article | - |
dc.identifier.doi | 10.1186/s12943-019-0972-8 | - |
dc.citation.journaltitle | Molecular Cancer | - |
dc.identifier.wosid | 000462941900013 | - |
dc.identifier.scopusid | 2-s2.0-85063750322 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 68 | - |
dc.citation.volume | 18 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Jeon, Sang-Min | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY | - |
dc.subject.keywordPlus | HUMAN BREAST | - |
dc.subject.keywordPlus | AGGRESSIVE PHENOTYPE | - |
dc.subject.keywordPlus | DRUG-RESISTANCE | - |
dc.subject.keywordPlus | SUPPORTIVE CARE | - |
dc.subject.keywordPlus | FIBROBLASTS | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | IL-6 | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordAuthor | Gastric cancer | - |
dc.subject.keywordAuthor | Cancer-associated fibroblasts | - |
dc.subject.keywordAuthor | Tumor microenvironment | - |
dc.subject.keywordAuthor | Chemo-resistance | - |
dc.subject.keywordAuthor | Interleukin-6 | - |
dc.subject.keywordAuthor | Tocilizumab | - |
dc.subject.keywordAuthor | Jak1-STAT3 | - |
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