Role of crosstalk between interleukin-6 and transforming growth factor-beta 1 in epithelial–mesenchymal transition and chemoresistance in biliary tract cancer
書誌事項
- 公開日
- 2013-05
- 資源種別
- journal article
- 権利情報
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- https://www.elsevier.com/tdm/userlicense/1.0/
- DOI
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- 10.1016/j.ejca.2012.12.002
- 公開者
- Elsevier BV
この論文をさがす
説明
The mechanisms of progression in biliary tract cancer (BTC) with inflammation, including epithelial-mesenchymal transition (EMT), are not well understood. We focused on two inflammation-associated cytokines, interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-β1), and investigated their expression and activity, as well as their relationship to key features of malignancy, in tumour samples from patients with BTC and in cultured BTC cells.We employed five BTC cell lines (MzChA-1, gemcitabine-resistant MzChA-1, HuCCT-1, KMCH and CCLP-1) to evaluate IL-6/TGF-β1 expression, tumour cell invasion, EMT and chemoresistance to gemcitabine in the presence or absence of recombinant human (rh) IL-6 and TGF-β1. Possible pathways were evaluated with specific pathway inhibitors and small interfering RNA (siRNA). We also used 20 resected specimens from patients with BTC to verify the results in vitro.IL-6 and TGF-β1 expression was associated with features of malignancy such as EMT and chemoresistance in the four BTC cell lines. Addition of rh IL-6 and TGF-β1 increased endogenous IL-6 and TGF-β1 expression through crosstalk and induced cell invasion, EMT and chemoresistance. Smad4 functioned in this process in a dominant manner, and inhibition by SMAD4 siRNA reduced IL-6 and TGF-β1 expression, blocked invasion, and reversed EMT and chemoresistance in cells exposed to rh IL-6 and TGF-β1 and in gemcitabine-resistant cells. Immunohistochemistry in resected specimens revealed IL6, TGF-β1, N-cadherin and Smad4 staining at the invasion front.Crosstalk between IL-6 and TGF-β1 is associated with malignant features, including EMT, and Smad4 works in a dominant manner to promote these features.
収録刊行物
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- European Journal of Cancer
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European Journal of Cancer 49 (7), 1725-1740, 2013-05
Elsevier BV
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キーワード
- Male
- Epithelial-Mesenchymal Transition
- Cell Survival
- Deoxycytidine
- Transforming Growth Factor beta1
- Cell Line, Tumor
- Humans
- Aged
- Smad4 Protein
- Interleukin-6
- Reverse Transcriptase Polymerase Chain Reaction
- Middle Aged
- Immunohistochemistry
- Gemcitabine
- Recombinant Proteins
- Gene Expression Regulation, Neoplastic
- Biliary Tract Neoplasms
- Drug Resistance, Neoplasm
- Female
- RNA Interference
詳細情報 詳細情報について
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- CRID
- 1360002215899616256
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- ISSN
- 09598049
-
- PubMed
- 23298711
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- 資料種別
- journal article
-
- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
