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Hepatocyte growth factor inhibits anoikis of pancreatic carcinoma cells through phosphatidylinositol 3-kinase pathway.
MedLine Citation:
PMID:  21499215     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: : Escape from anoikis, apoptosis induced by loss of cell-cell or cell-extracellular matrix interactions, is important in tumor invasion and metastasis. Hepatocyte growth factor (HGF) is known to play a pivotal role in pancreatic carcinomas. This study aimed to determine the antianoikis effect of HGF in pancreatic carcinoma cells.
METHODS: : Antianoikis effect of HGF was evaluated in human pancreatic carcinoma cells in nonadherent culture with or without anti-E-cadherin antibody. Signal pathways were investigated by Western blot analysis and inhibition assay using inhibitors for phosphatidylinositol 3-kinase and p38.
RESULTS: : Pancreatic carcinoma cells underwent anoikis in nonadherent culture. However, some of the carcinoma cells survived by forming aggregations in suspension. Anti-E-cadherin antibody dissociated the aggregations, and the separated cells underwent additional anoikis. Hepatocyte growth factor inhibited anoikis irrespective of E-cadherin-mediated cell-cell contact. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway abolished the antianoikis effect of HGF. Phosphorylation of Akt was induced by HGF, and the phosphorylated Akt persisted even when E-cadherin was inhibited.
CONCLUSIONS: : Hepatocyte growth factor inhibits anoikis of pancreatic carcinoma cells through phosphatidylinositol 3-kinase pathway in which activation of Akt may be involved. It is thus supposed that HGF may have a potent role in invasion and metastasis of pancreatic carcinoma cells by exerting its antianoikis effect.
Authors:
Satoshi Watanabe; Takashi Kishimoto; Osamu Yokosuka
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pancreas     Volume:  40     ISSN:  1536-4828     ISO Abbreviation:  Pancreas     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8608542     Medline TA:  Pancreas     Country:  United States    
Other Details:
Languages:  eng     Pagination:  608-14     Citation Subset:  IM    
Affiliation:
From the Departments of *Medicine and Clinical Oncology and †Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
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