icam-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastomaicam-2表达介导membrane-actin链接时,授予nonmetastatic表型和反映了良好的肿瘤阶段或在神经母细胞瘤组织学.pdfVIP

ICAM-2 Expression Mediates a Membrane-Actin Link, Confers a Nonmetastatic Phenotype and Reflects Favorable Tumor Stage or Histology in Neuroblastoma 1 1 1 1 2 Karina Jin Yoon *, Doris A. Phelps , Rebecca A. Bush , Joanna S. Remack , Catherine A. Billups , Joseph D. Khoury3 1 Department of Molecular Pharmacology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 2 Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America, 3 Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, United States of America Abstract The actin cytoskeleton is a primary determinant of tumor cell motility and metastatic potential. Motility and metastasis are thought to be regulated, in large part, by the interaction of membrane proteins with cytoplasmic linker proteins and of these linker proteins, in turn, with actin. However, complete membrane-to-actin linkages have been difficult to identify. We used co-immunoprecipitation and competitive peptide assays to show that intercellular adhesion molecule-2 (ICAM-2)/a- actinin/actin may comprise such a linkage in neuroblastoma cells. ICAM-2 expression limited the motility of these cells and redistributed actin fibers in vitro, and suppressed development of disseminated tumors in an in vivo model of metastatic neuroblastoma. Consistent with these observations, immunohistochemical analysis demonstrated ICAM-2 expression in primary neuroblastoma tumors exhibiting features that are associated with limited metastatic disease and more favorable clinical outcome. In neuroblastoma cell lines, ICAM-2 expression did not affect AKT activation, tumorigenic potential or chemosensitivity, as has been