title: Integrin β1 is critical for gastrin-releasing peptide receptor-mediated neuroblastoma cell migration and invasion.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sora
authors.initials: S
authors.lastname: Lee
authors.forename: Jingbo
authors.initials: J
authors.lastname: Qiao
authors.forename: Pritha
authors.initials: P
authors.lastname: Paul
authors.forename: Dai H
authors.initials: DH
authors.lastname: Chung
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology; D006801:Humans; D039421:Integrin alpha2 / Q000032:analysis; D039422:Integrin alpha3 / Q000032:analysis; D019012:Integrin beta1 / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009447:Neuroblastoma / Q000473:pathology*; D018004:Receptors, Bombesin / Q000502:physiology*
chemical_list: D039421:Integrin alpha2; D039422:Integrin alpha3; D019012:Integrin beta1; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide
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