Interleukin 23 promotes hepatocellular carcinoma metastasis via NF-kappa B induced matrix metalloproteinase 9 expression.
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most popular cancers in the world with poor prognosis, which often develops from chronic liver inflammatory diseases. Interleukin 23 (IL-23) is an inflammatory cytokine which is reported to play an important role in tumor development in animal model. While the function of IL-23 in HCC development remains unknown, so we investigate the role of IL-23 in HCC progression in this study.


RESULTS
Transcript level of IL-23, interleukin17A (IL-17A) and matrix metalloproteinases 9 (MMP9) in clinical HCC samples (n=81) was determined by qPCR. Protein expression pattern of IL-23 in primary and metastatic HCC tissues pairs (n=49 pairs) was determined by immunohistochemistry staining. Cell migration, invasion, RNA interfering and immune blotting were used to characterize the functional and signaling mechanisms in IL-23-treated HCC. Compared with paired non-tumor tissue, higher IL-23 expression was detected in HCC tumor tissues with metastasis. Immunohistochemistry staining confirmed the high expression of IL-23 in metastasis HCC. Immune blotting demonstrated that IL-23 was highly expressed in HCC cell lines with metastasis. Functional study found that IL-23 could promote HCC cell migration and invasion. Molecular analysis revealed that IL-23 could upregulate MMP9 expression via NF-κB/p65 signaling activation and IL-17A could improve IL-23 expression in tumor cells directly via activating NF-κB/p65 signaling pathway.


CONCLUSIONS
IL-23 could promote HCC metastasis by the upregulation of MMP9 expression via activating NF-κB/p65 signaling pathway. At the same time, IL-17A could further promote IL-23 expression in HCC tumor cells.
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Jian
J
Li
George
G
Lau
Leilei
L
Chen
Yun-Fei
YF
Yuan
Jun
J
Huang
John M
JM
Luk
Dan
D
Xie
Xin-Yuan
XY
Guan
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D016133:Polymerase Chain Reaction
D020381:Interleukin-17; D053759:Interleukin-23; D016328:NF-kappa B; D020780:Matrix Metalloproteinase 9