Integrin expression regulates neuroblastoma attachment and migration.
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.
Meyer
Amy
A
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
van Golen
Cynthia M
CM
Kim
Bhumsoo
B
van Golen
Kenneth L
KL
Feldman
Eva L
EL
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics* / Q000502:physiology; D016023:Integrins / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology* / Q000503:physiopathology; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D019012:Integrin beta1; D016023:Integrins; D017526:Receptor, IGF Type 1