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

// Jun Long 1 , Hongyan Guo 2 , Shichang Cui 3 , Haiyan Zhang 4 , Xinmin Liu 1 , Danning Li 1 , Zimeng Han 1 , Linfeng Xi 1 , Wenyi Kou 1 , Jiangnan Xu 1 , Tao-Sheng Li 5 , Yaozhong Ding 1 1 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, P.R. China 2 Clinical Laboratory of Beijing Youan Hospital, Capital Medical University, Beijing, 100069, P.R. China 3 Oncology and Hepatobiliary Minimally Invasive Interventional Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, P.R. China 4 Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, 100069, P.R. China 5 Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan Correspondence to: Jun Long, email: longjunj@ccmu.edu.cn Jiangnan Xu, email: xujn@ccmu.edu.cn Tao-Sheng Li, email: litaoshe@nagasaki-u.ac.jp Yaozhong Ding, email: dingyz@ccmu.edu.cn Keywords: IL-35, hepatocellular carcinoma, tumor progression, migration, invasion Received: March 01, 2016      Accepted: June 03, 2016      Published: June 17, 2016 ABSTRACT 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.