BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis. METHODS: We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis. RESULTS: OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue. CONCLUSIONS: These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential.
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis. METHODS: We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis. RESULTS:OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rathepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue. CONCLUSIONS: These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential.
Authors: Patrick A Ott; Omid Hamid; Anna C Pavlick; Harriet Kluger; Kevin B Kim; Peter D Boasberg; Ronit Simantov; Elizabeth Crowley; Jennifer A Green; Thomas Hawthorne; Thomas A Davis; Mario Sznol; Patrick Hwu Journal: J Clin Oncol Date: 2014-09-29 Impact factor: 44.544
Authors: Oneida A Arosarena; Fabiola E Del Carpio-Cano; Raul A Dela Cadena; Mario C Rico; Emeka Nwodim; Fayez F Safadi Journal: J Cell Physiol Date: 2011-11 Impact factor: 6.384
Authors: April A N Rose; Matthew G Annis; Zhifeng Dong; Francois Pepin; Michael Hallett; Morag Park; Peter M Siegel Journal: PLoS One Date: 2010-08-10 Impact factor: 3.240
Authors: E Anders Kolb; Richard Gorlick; Catherine A Billups; Thomas Hawthorne; Raushan T Kurmasheva; Peter J Houghton; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2014-06-09 Impact factor: 3.167
Authors: Adamantios Michalinos; Alexandra K Tsaroucha; Maria Lambropoulou; Dimitrios Schizas; Georgia Valsami; Nikolaos Kostomitsopoulos; Michael S Pitiakoudis; Constantinos E Simopoulos Journal: Transl Gastroenterol Hepatol Date: 2020-01-05