Integrin β1 is critical for gastrin-releasing peptide receptor-mediated neuroblastoma cell migration and invasion.

Lee S, Qiao J, Paul P, Chung DH
Surgery. 2013 154 (2): 369-75

PMID: 23889963 · PMCID: PMC4313735 · DOI:10.1016/j.surg.2013.04.067

BACKGROUND - Gastrin-releasing peptide (GRP) and its receptor, GRP-R, are critically involved in neuroblastoma tumorigenesis; however, the molecular mechanisms and signaling pathways that are responsible for GRP/GRP-R-induced cell migration and invasion remain unclear. In this study, we sought to determine the cell signals involved in GRP/GRP-R-mediated neuroblastoma cell migration and invasion.

METHODS - Human neuroblastoma cell lines SK-N-SH, LAN-1, and IMR-32 were used for our study. Transwell migration and invasion assays were performed after GRP (10(-7) M) stimulation. The cDNA GEArray Microarray kit was used to determine GRP-R-induced gene expression changes. Protein and membrane expression of integrin subunits were confirmed by Western blotting and flow cytometry analysis. siRNA transfection was performed using Lipofectamine 2000. For scratch assay, a confluent monolayer of cells in 6-well plates were wounded with micropipette tip and observed microscopically at 24 to 72 h.

RESULTS - GRP increased neuroblastoma cell migration and expressions of MMP-2 whereas the TIMP-1 level decreased. GRP-R overexpression stimulated SK-N-SH cell migration and upregulated integrin α2, α3, and β1 protein as well as mRNA expression. Targeted silencing of integrin β1 inhibited cell migration.

CONCLUSION - GRP/GRP-R signaling contributes to neuroblastoma cell migration and invasion. Moreover, the integrin ß1 subunit critically regulates GRP-R-mediated neuroblastoma cell migration and invasion.

Copyright © 2013 Mosby, Inc. All rights reserved.

MeSH Terms (10)

Cell Line, Tumor Cell Movement Gastrin-Releasing Peptide Humans Integrin alpha2 Integrin alpha3 Integrin beta1 Neoplasm Invasiveness Neuroblastoma Receptors, Bombesin

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