Interleukin-6 trans-signaling increases the expression of carcinoembryonic antigen-related cell adhesion molecules 5 and 6 in colorectal cancer cells

BMC Cancer

Research Article

Georg H. Wätzig¹  Holger Kalthoff²  Reinhild Holmer²  Stefan Rose-John³  Sanjay Tiwari⁴ 

[1] CONARIS Research Institute AG, Kiel, Germany;Division of Molecular Oncology, Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, 24105, Kiel, Germany;Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany;Section Biomedical Imaging, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, Germany;

关键词: IL-6;    Hyper-IL-6;    Trans-signaling;    CEA;    Inflammation;    Tumor-associated antigens;    Tumor marker;    Colon cancer;    Colitis-associated cancer;   

DOI  :  10.1186/s12885-015-1950-1

 received in 2015-07-17, accepted in 2015-11-23,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) is among the five most frequent causes for cancer-related deaths in Europe. One of the most important tumor-associated antigens for CRC is carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), which is involved in cell adhesion, migration, anoikis, tumor invasion and metastasis. Its family member CEACAM6 is also upregulated in adenomas and carcinomas of the colon and an independent predictor of poor survival. Previous studies have reported a link between upregulation of CEACAM5 and interleukin-6 (IL-6). IL-6 plays an important role in CRC progression, and signaling is mediated via two pathways (classic and trans-signaling). However, this link could not be confirmed by other studies, and the role of IL-6 trans-signaling in the CEACAM5 upregulation has not been elucidated. Moreover, the impact of IL-6 on the expression of CEACAM6 has not yet been examined.MethodsThe expression of IL-6, IL-6 receptor (IL-6R), glycoprotein (gp) 130, CEACAM5 and CEACAM6 was analyzed by RT-PCR, Western blot, flow cytometry or qPCR. Colon cell lines were incubated with IL-6 or Hyper-IL-6 (mediating IL-6 trans-signaling), and subsequently, the expression of CEACAMs was determined by qPCR or Western blot. FLLL31, an inhibitor of the phosphorylation of signal transducer and activator of transcription-3 (STAT3), was used to determine the role of STAT3 phosphorylation.ResultsWe confirmed that colon carcinoma cell lines express IL-6 and IL-6R. We observed only a weak upregulation of CEACAM5 and CEACAM6 by classic IL-6 signaling, but a strong increase by IL-6 trans-signaling. This upregulation depended on the phosphorylation of STAT3.ConclusionsOur data show the upregulation of the tumor-associated antigens CEACAM5/6 by trans-signaling of the pro-inflammatory cytokine IL-6. This mechanism may contribute to the tumor-promoting role of IL-6 and could therefore be a target for therapeutic intervention in particular by specific inhibitors such as sgp130Fc.

【 授权许可】

CC BY   
© Holmer et al. 2015