In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 247-247
Abstract:
247 Background: Biliary tract cancer (BTC) is well-known to be commonly suffered from inflammations; cholangitis and/or liver abscess. The author previously showed interleukin-6 (IL-6) worked on anti-apoptotic process in BTC. Herein, we focused on inflammation-associated cytokines including not only IL-6 but also transforming growth factor-beta 1 (TGF-β1), and investigated the working processes, their relationship to chemoresistance, and therapeutic implications. Methods: We employed resected specimens and BTC cell lines. We evaluated IL-6/TGF-β1 expression, invasion, endothelial-mesenchymal transition (EMT), and chemoresistance to gemcitabine, with or without silencing of PI3K/Akt, MAPK, STAT, and Smad pathways. Results: Resected specimens expressed IL6 and TGF-β1 staining at the invasion front by immunohistochemical staining. In BTC cell lines, spontaneous expression of IL-6/TGF-β1 was related to malignant potencies such as EMT and chemoresistance. Rh IL-6/TGF-β1 induced invasion, EMT, and chemoresistance. Smad4 among cell signaling pathways functioned in a dominant manner; inhibition of Smad4 pathway reduced invasion, and reversed EMT and chemoresistance, in both rh IL-6/TGF-β1-treated cells, and we confirmed these results using SMAD4 siRNA. And, our established gemcitabine-resistant cells expressed high level of IL-6/TGF-β1, and promoted EMT. Inhibition of Smad4 also reversed chemoresistance in gemcitabine-resistant cells. We confirmed N-cadherin and Smad4 expression at the invasion front by immunohistochemistry. Conclusions: IL-6 and TGF-β1 resulted in chemoresistance, and inhibition of Smad4 would reverse chemoresistance in BTC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2014.32.3_suppl.247
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2014
detail.hit.zdb_id:
2005181-5
