Hepatocyte growth factor inhibits anoikis of pancreatic carcinoma cells through phosphatidylinositol 3-kinase pathway.

Abstract

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
• Journal: Pancreas (Pancreas) Vol. 40 Issue 4 Pg. 608-14 (May 2011) ISSN: 1536-4828 [Electronic] United States
• PMID: 21499215 (Publication Type: Journal Article)

Chemical References

• Androstadienes
• Antibodies
• Cadherins
• Enzyme Inhibitors
• Imidazoles
• Phosphoinositide-3 Kinase Inhibitors
• Pyridines
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Anoikis (drug effects)
• Antibodies (immunology, pharmacology)
• Blotting, Western
• Cadherins (immunology, metabolism)
• Cell Adhesion (drug effects)
• Cell Communication (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival
• Enzyme Inhibitors (pharmacology)
• Hepatocyte Growth Factor (pharmacology)
• Humans
• Imidazoles (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyridines (pharmacology)
• Signal Transduction (drug effects)
• Wortmannin
• Xenograft Model Antitumor Assays
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)