title: Interleukin-6 enhances cancer stemness and promotes metastasis of hepatocellular carcinoma via up-regulating osteopontin expression.
abstract: Interleukin-6 (IL-6), one of the most important inflammatory cytokines, plays a pivotal role in metastasis and stemness of solid tumors. However, the underlying mechanisms of IL-6 in HCC metastasis remain unclear. In the present study, we demonstrated that stemness and metastatic potential of HCC cells were significantly enhanced after IL-6 stimulation. IL-6 could induce expression of osteopontin (OPN), along with other stemness-related genes, including HIF1α, BMI1, and HEY1. Block of OPN induction could significantly abrogate the effect of IL-6 on stemness and metastasis of HCC cells. Furthermore, IL-6 level was positively correlated with OPN in HCC. Patients with high plasma IL-6 or OPN level had poorer prognosis. In multivariate analysis, IL-6 and OPN were demonstrated to be independent prognostic indicators for HCC patients, and their combination had a better prognostic performance than IL-6 or OPN alone. Collectively, our findings indicate that IL-6 could enhance stemness and promote metastasis of HCC via up-regulating OPN expression, which can be a potential therapeutic target for combating HCC metastasis, and the combination of IL-6 and OPN serves as a promising prognostic predictor for HCC.
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University 12 Urumqi Road (M), Shanghai 200040, China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University 12 Urumqi Road (M), Shanghai 200040, China.
authors.forename: Hao-Ting
authors.initials: HT
authors.lastname: Sun
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, 180 Feng Lin Road, Fudan University Shanghai 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sheng
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University 12 Urumqi Road (M), Shanghai 200040, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Jin-Wang
authors.initials: JW
authors.lastname: Wei
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Zhang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University 12 Urumqi Road (M), Shanghai 200040, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institutes of Biomedical Sciences, Fudan University 131 Dong An Road, Shanghai 200032, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University 12 Urumqi Road (M), Shanghai 200040, China.
authors.forename: Lu-Yu
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University12 Urumqi Road (M), Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University131 Dong An Road, Shanghai 200032, China.
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Huanshan Hospital, Cancer Metastasis Institute, Fudan University12 Urumqi Road (M), Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University131 Dong An Road, Shanghai 200032, China.
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
keywords: Liver cancer; cancer stem cell; inflammatory factor; prognosis