Faculty Collaboration Database

Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells. Mol Cancer Ther 2006 Jul;5(7):1676-82

Date

08/08/2006

Pubmed ID

16891453

DOI

10.1158/1535-7163.MCT-05-0175

Scopus ID

2-s2.0-33748310896 (requires institutional sign-in at Scopus site)   96 Citations

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.

Author List

Bauer TW, Somcio RJ, Fan F, Liu W, Johnson M, Lesslie DP, Evans DB, Gallick GE, Ellis LM

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Carcinoma
Cell Movement
Hepatocyte Growth Factor
Humans
Insulin-Like Growth Factor I
Neoplasm Invasiveness
Pancreatic Neoplasms
Phosphorylation
Proto-Oncogene Proteins c-met
Receptor, IGF Type 1