Research Papers:

IL-35 expression in hepatocellular carcinoma cells is associated with tumor progression

Jun Long, Hongyan Guo, Shichang Cui, Haiyan Zhang, Xinmin Liu, Danning Li, Zimeng Han, Linfeng Xi, Wenyi Kou, Jiangnan Xu, Tao-Sheng Li and Yaozhong Ding _

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Oncotarget. 2016; 7:45678-45686. https://doi.org/10.18632/oncotarget.10141

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Jun Long1, Hongyan Guo2, Shichang Cui3, Haiyan Zhang4, Xinmin Liu1, Danning Li1, Zimeng Han1, Linfeng Xi1, Wenyi Kou1, Jiangnan Xu1, Tao-Sheng Li5, Yaozhong Ding1

1Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, P.R. China

2Clinical Laboratory of Beijing Youan Hospital, Capital Medical University, Beijing, 100069, P.R. China

3Oncology and Hepatobiliary Minimally Invasive Interventional Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, P.R. China

4Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, 100069, P.R. China

5Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan

Correspondence to:

Jun Long, email: [email protected]

Jiangnan Xu, email: [email protected]

Tao-Sheng Li, email: [email protected]

Yaozhong Ding, email: [email protected]

Keywords: IL-35, hepatocellular carcinoma, tumor progression, migration, invasion

Received: March 01, 2016     Accepted: June 03, 2016     Published: June 17, 2016


IL-35 has recently been demonstrated to play significant roles in the progression of various malignant tumors. We investigated the expression of IL-35 in hepatocellular carcinoma (HCC) and the regulatory mechanisms in HCC progression. Tissue microarray from 75 HCC patients revealed that IL-35 was primarily localized in the cytoplasm of cancer cells and peri-tumoral hepatocytes. Quantitative analysis showed that IL-35 expression was significantly lower in patients in the advanced stages than in the early stages. Significantly lower expression of IL-35 was also observed in HCC patients with higher histological grades, larger tumor size, positive microvascular invasion and lymph node/distant metastasis. IL-35 over-expression in HepG2 cells significantly upregulated HLA-ABC and CD95, reduced activities of MMP-2 and MMP-9, and decreased cell migration, invasion and colony formation capacities. Our data indicated that decreased expression of IL-35 in tumor tissues might contribute to the progression of HCC, and IL-35 may serve as a new therapeutic target for HCC.

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