Integrin expression regulates neuroblastoma attachment and migration

Neoplasia. Jul-Aug 2004;6(4):332-42. doi: 10.1593/neo.03445.

Abstract

Neuroblastoma (NBL) is the most common malignant disease of infancy, and children with bone metastasis have a mortality rate greater than 90%. Two major classes of proteins, integrins and growth factors, regulate the metastatic process. We have previously shown that tumorigenic NBL cells express higher levels of the type I insulin-like growth factor receptor (IGF-IR) and that beta1 integrin expression is inversely proportional to tumorigenic potential in NBL. In the current study, we analyze the effect of beta1 integrin and IGF-IR on NBL cell attachment and migration. Nontumorigenic S-cells express high levels of beta1 integrin, whereas tumorigenic N-cells express little beta1 integrin. Alterations in beta1 integrin are due to regulation at the protein level, as translation is decreased in N-type cells. Moreover, inhibition of protein synthesis shows that beta1 integrin is degraded more slowly in S-type cells (SHEP) than in N-type cells (SH-SY5Y and IMR32). Inhibition of alpha5beta1 integrin prevents SHEP (but not SH-SY5Y or IMR32) cell attachment to fibronectin and increases SHEP cell migration. Increases in IGF-IR decrease beta1 integrin expression, and enhance SHEP cell migration, potentially through increased expression of alphavbeta3. These data suggest that specific classes of integrins in concert with IGF-IR regulate NBL attachment and migration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin beta1 / genetics*
  • Integrin beta1 / physiology
  • Integrins / physiology
  • Neuroblastoma / pathology*
  • Neuroblastoma / physiopathology
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • Integrin beta1
  • Integrins
  • Receptor, IGF Type 1