Document Detail


Overexpression of SPARC obliterates the in vivo tumorigenicity of human hepatocellular carcinoma cells.
MedLine Citation:
PMID:  19830689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. Current treatments are extremely disappointing. SPARC (Secreted protein, acidic and rich in cysteine) is a matricellular glycoprotein with differential expression in several tumors, including HCC, which significance remains unclear. We infected HCC cells (HepG2, Hep3B and Huh7) with an adenovirus expressing SPARC (AdsSPARC) to examine the role of SPARC expression on HCC cells and its effect on tumor aggressiveness. The in vitro HCC cells substrate-dependent proliferation and cell cycle profile were unaffected; however, SPARC overexpression reduced HCC proliferation when cells were grown in spheroids. A mild induction of cellular apoptosis was observed upon SPARC overexpression. SPARC overexpression resulted in spheroid growth inhibition in vitro while no effects were found when recombinant SPARC was exogenously applied. Moreover, the clonogenic and migratory capabilities were largely decreased in SPARC-overexpressing HCC cells, altogether suggesting a less aggressive HCC cell phenotype. Consistently, AdsSPARC-transduced cells showed increased E-cadherin expression and a concomitant decrease in N-cadherin expression. Furthermore, SPARC overexpression was found to reduce HCC cell viability in response to 5-FU-based chemotherapy in vitro, partially through induction of apoptosis. In vivo experiments revealed that SPARC overexpression in HCC cells inhibited their tumorigenic capacity and increased animal survival through a mechanism that partially involves host macrophages. Our data suggest that SPARC overexpression in HCC cells results in a reduced tumorigenicity partially through the induction of mesenchymal-to-epithelial transition (MET). These evidences point to SPARC as a novel target for HCC treatment.
Authors:
Catalina Atorrasagasti; Mariana Malvicini; Jorge B Aquino; Laura Alaniz; Mariana Garcia; Marcela Bolontrade; Manglio Rizzo; Osvaldo L Podhajcer; Guillermo Mazzolini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  126     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-03-30     Completed Date:  2010-04-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2726-40     Citation Subset:  IM    
Affiliation:
Gene Therapy Laboratory, Liver Unit School of Medicine, Austral University, Av. Presidente Per?n 1500, (B1629ODT) Derqui-Pilar, Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Apoptosis
Carcinoma, Hepatocellular / genetics,  pathology*
Cell Cycle / drug effects
Cell Division / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Cell Survival / drug effects
Colony-Forming Units Assay
Gene Expression Regulation, Neoplastic
Genetic Vectors
Humans
Liver Neoplasms / genetics,  pathology*
Osteonectin / genetics*,  pharmacology
Recombinant Proteins / pharmacology
Chemical
Reg. No./Substance:
0/Osteonectin; 0/Recombinant Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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