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Cited by 264

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

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

Open access
Ham, In-Hye, Oh, Hye Jeong, Jin, Hyejin, Bae, Cheong A, Jeon, Sang-Min, Choi, Kyeong Sook, Son, Sang-Yong, Han, Sang-Uk, Brekken, Rolf A., Lee, Dakeun, Hur, Hoon·2019·Molecular Cancer
DOI 10.1186/s12943-019-0972-8
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Abstract

BACKGROUND: Although 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. METHODS: To 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. RESULTS: Secretome 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. CONCLUSIONS: Our 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.

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Metadata

Authors
Ham, I.-H., Oh, H. J., Jin, H., Bae, C. A., Jeon, S.-M., Choi, K. S., Son, S.-Y., Han, S.-U., Brekken, R. A., Lee, D., & Hur, H.
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2019-03-30
Volume
18
Issue
1
Pages
68-68
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-019-0972-8
OpenAlex
W2942680788
Cited by
264
References
52
FWCI
19.27
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer. https://app.cochat.ai/papers/10.1186/s12943-019-0972-8
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Ham, I.-H., Oh, H. J., Jin, H., Bae, C. A., Jeon, S.-M., Choi, K. S., Son, S.-Y., Han, S.-U., Brekken, R. A., Lee, D., & Hur, H. (2019). Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer. Molecular Cancer. https://doi.org/10.1186/s12943-019-0972-8

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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