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, integrin expression is inversely proportional to tumorigenic potential in NBL. In the current study, we analyze the effect of, integrin and IGF-IR on NBL cell attachment and migration. Nontumorigenic S-cells express high levels of beta(1) integrin, whereas tumorigenic N-cells express little beta(1) integrin. Alterations in beta(1) integrin are due to regulation at the protein level, as translation is decreased in N-type cells. Moreover, inhibition of protein synthesis shows that beta(1) integrin is degraded more slowly in S-type cells (SHEP) than in N-type cells (SH-SY5Y and IMR32). Inhibition Of alpha(5)beta(1) integrin prevents SHEP (but not SH-SY5Y or IMR32) cell attachment to fibronectin and increases SHEP cell migration. Increases in IGF-IR decrease beta(1) integrin expression, and enhance SHEP cell migration, potentially through increased expression Of alpha(v)beta(3). These data suggest that specific classes of integrins in concert with IGF-IR regulate NBL attachment and migration.