Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells.

Abstract

Pancreatic carcinoma cells overexpress the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and the hepatocyte growth factor (HGF) receptor, c-Met, which are both known to mediate tumor cell migration and invasion. We hypothesized that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells and that IGF-I-mediated migration and invasion depend on c-Met. Migration and invasion assays were done with the human pancreatic cancer cell line L3.6pl treated with PBS, IGF-I, HGF, or IGF-I plus HGF. To determine if c-Met is necessary for IGF-IR-mediated migration and invasion, c-Met was down-regulated in L3.6pl cells via adenoviral infection with a c-Met ribozyme before IGF-I treatment. IGF-I and HGF increased cell migration and invasion. Furthermore, IGF-I plus HGF had a greater than additive effect on cell migration and invasion compared with either growth factor alone. Down-regulation of c-Met nearly completely inhibited IGF-I-mediated migration and invasion. Our findings suggest that IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells. Furthermore, c-Met is required for both HGF- and IGF-I-mediated migration and invasion. Elucidation of the signaling pathways that contribute to tumor progression and metastasis should provide a foundation for the development of targeted therapies for pancreatic carcinoma.

• Authors: Todd W Bauer, Ray J Somcio, Fan Fan, Wenbiao Liu, Marjorie Johnson, Donald P Lesslie, Douglas B Evans, Gary E Gallick, Lee M Ellis
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 5 Issue 7 Pg. 1676-82 (Jul 2006) ISSN: 1535-7163 [Print] United States
• PMID: 16891453 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hepatocyte Growth Factor
• Insulin-Like Growth Factor I
• Proto-Oncogene Proteins c-met
• Receptor, IGF Type 1

Topics

• Carcinoma (metabolism, pathology)
• Cell Movement (drug effects)
• Hepatocyte Growth Factor (pharmacology)
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• Neoplasm Invasiveness
• Pancreatic Neoplasms (metabolism, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-met (antagonists & inhibitors, metabolism)
• Receptor, IGF Type 1 (metabolism)