A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. A worldwide increase in mortality associated with hepatocellular carcinoma (HCC) has recently been reported. 1,2 Clinical treatment of HCC remains challenging due to a high incidence of tumor recurrence. The main cause of death in HCC patients is intrahepatic metastasis but the underlying mechanisms are still not fully understood. It is generally believed that to give rise to a metastatic tumor, cancer cells from a primary site must complete all of the following steps: invasion, intravasation, survival and arrest in the blood stream, extravasation, and colonization at a new site. The motility of cancer cells, driven by the actin cytoskeleton network, has been well documented to play crucial roles at multiple steps during the metastasis process.

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Amplification of SEI-1, a cell cycle regulatory gene at 19q13.1, is commonly detected in ovarian cancer, suggesting a role in the pathogenesis of ovarian cancer. In the present study, the oncogenic potential of SEI-1 was shown by anchorageindependent growth and tumor formation in nude mice with SEI-1-transfected NIH 3T3 mouse fibroblast cells. Silencing of SEI-1 gene expression by small interfering RNAs in ovarian cancer cell line SKOV3 could inhibit cell growth as well as colony formation on soft agar. Chromosomal alterations including the formation of double minutes were observed in tumor cells derived from SEI-1-transformed NIH 3T3 cells. Micronulei formation, which is an indicator of nuclear abnormality and genomic instability, was markedly increased in SEI-1 -transfected cells. These data suggest that the oncogenic role of SEI-1 might be mediated at least in part via an effect on genomic instability. Furthermore, overexpression of SEI-1 was associated with higher tumor grades and late Fesddration Internationale des Gynaecologistes et Obstetristes (FIGO) stages in ovarian carcinomas. These data strongly suggest that SEI-1 plays an important role in the development and progression of ovarian cancer. (Cancer Res 2005; 65(15): 6504-8)

Chronic pancreatitis/pancreatic cancer (CP/PC) is characterized by fibrous connective tissue proliferation induced by activated pancreatic stellate cells (PSCs). Galectin-1 is upregulated in activated PSCs and is important for the continuing activation of PSCs. The aim of this study was to evaluate the effect of galectin-1 derived from activated PSCs on the progression of fibrosis in CP/PC. To this end, the expression of desmin, α-SMA, galectin-1, fibronectin and collagen type I in normal pancreatic, CP and PC tissues, as well as quiescent/activated PSCs, was investigated. The proliferation rate and migration ability of control, galectin-1-overexpressing and galectin-1-silenced PSCs were also evaluated, as well as the mRNA and protein expression of fibronectin, collagen type I, α-SMA, tissue inhibitors of metalloproteinases (TIMP)-1, MMP-2, Smad2 and TGF-β1. Furthermore, the effect of adding a TGF-β1 receptor inhibitor on the expression of these proteins was examined. The results revealed that the expression profile of desmin, α-SMA, galectin-1, fibronectin and collagen type I in the normal pancreas was similar to that of quiescent PSCs and the expression profile in CP/PC tissues was similar to that of activated PSCs. Furthermore, galectin-1-overexpressing PSCs exhibited a significantly higher proliferation rate and migration ability, while galectin-1-silenced PSCs exhibited a significantly lower proliferation rate and migration ability than the control PSCs. The expression of fibronectin, collagen type I, α-SMA, MMP-2 and TIMP-1 was also significantly higher in the galectin-1-overexpressing PSCs than the control PSCs and this effect was found to be mediated by the TGF-β1/Smad pathway. The trends in the expression of these factors were reversed in the galectin-1-silenced PSCs. From these findings, it can be concluded that overexpression of galectin-1 promotes PSC activity (proliferation and migration) and stimulates fibrosis by increasing extracellular matrix synthesis and decreasing the MMP/TIMP ratio via the TGF-β1/Smad pathway. Thus, galectin-1 may be a novel candidate for reversing or halting fibrosis progression in CP/PC.