Clusterin plays an important role in hepatocellular carcinoma metastasis

Abstract

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, Po0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (Po0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread

“…Further evidence that CLU might be oncogenic is that it can bind to and inactivate BAX, inhibiting druginduced apoptosis, and cooperate with c-MYC in transforming mammalian cells (Zhang et al, 2005). A tumourigenic effect of CLU in other types of epithelial cancer, like hepatocellular carcinoma, has been observed (Lau et al, 2006). In contrast with the hypothesis that CLU is a prostate oncogene, we and others have observed that CLU is down-regulated during human prostate cancer progression Rauhala et al, 2008).…”

Differential expression of haptoglobin isoforms in chronic active hepatitis, cirrhosis and HCC related to HBV infection

“…In HCC, CLU may play a significant role in tumorigenesis, progression and metastasis (25). Increased serum levels of CLU have been reported in lung cancer, breast cancer, ovarian cancer and HCC (8,24,(26)(27)(28). Ficolin belongs to the serum lectins and plays a crucial role in innate immunity.…”

Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma

“…Cancer metastases, both intrahepatic and extrahepatic, are major factors causing the mortality of HCC patients. Recently, a number of cancer genes have been reported to be associated with the tumor metastasis in HCC, including CLU, KAI1, ROCK2 and TWIST [1][2][3][4]. Furthermore, we have previously identified several microRNAs that play critical roles in HCC metastasis, such as miR-30D, miR-151 and miR-210 [5][6][7].…”