title: Modeling of Hepatocytes Proliferation Isolated from Proximal and Distal Zones from Human Hepatocellular Carcinoma Lesion.
abstract: Isolation of hepatocytes from cirrhotic human livers and subsequent primary culture are important new tools for laboratory research and cell-based therapeutics in the study of hepatocellular carcinoma (HCC). Using such techniques, we have previously identified different subpopulations of human hepatocytes and among them one is showing a progressive transformation of hepatocytes in HCC-like cells. We have hypothesized that increasing the distance from the neoplastic lesion might affect hepatocyte function and transformation capacity. However, limited information is available in comparing the growth and proliferation of human hepatocytes obtained from different areas of the same cirrhotic liver in relation to their distance from the HCC lesion. In this study, hepatocytes from 10 patients with cirrhosis and HCC undergoing surgical resections from specimens obtained at a proximal (CP) and distal (CD) distance from the HCC lesion were isolated and placed in primary culture. CP hepatocytes (CP-Hep) were isolated between 1 to 3 cm (leaving at least 1cm margin to avoid cancer cells and/or satellite lesions), while CD hepatocytes (CD-Hep) were isolated from more than 5 cm or from the contralateral-lobe. A statistical model was built to analyze the proliferation rates of these cells and we evaluated expression of HCC markers (Glypican-3 (GPC3), αSmooth Muscle Actin (α-SMA) and PCNA). We observed a significant difference in proliferation and in-vitro growth showing that CP-Hep had a proliferation pattern and rate significantly different than CD-Hep. Based on these data, this model can provide information to predict growth of human hepatocytes in primary culture in relation to their pre-cancerous state with significant differences in the HCC markers expression. This model provides an important innovative tool for in-vitro analysis of HCC.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas, United States of America.|Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Via del Vespro 129, Polyclinic, 90127 Palermo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Montalbano
authors.affiliation: Department of Chemical, Management, Informatics and Mechanical Engineering, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curcurù
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Shirafkan
authors.affiliation: Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Polyclinic, University of Palermo, Palermo, Italy.|Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Biotechnology, Temple University, Philadelphia, PA, United States of America.
authors.forename: Renza
authors.initials: R
authors.lastname: Vento
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Rastellini
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Luca
authors.initials: L
authors.lastname: Cicalese
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured