ICAM-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastoma
| Autor: | Joseph Khoury, Joanna S. Remack, Rebecca A. Bush, Karina J. Yoon, Doris A. Phelps, Catherine A. Billups |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Non-Clinical Medicine Transplantation Heterologous Pediatrics and Child Health Motility lcsh:Medicine Mice SCID Actinin Biology Biochemistry Mice Neuroblastoma Antigens CD Cell Movement Tumor Cells Cultured medicine Animals Humans Neoplasm Metastasis Child lcsh:Science Molecular Biology Protein kinase B Actin Neoplasm Staging Multidisciplinary Cell adhesion molecule Cell Membrane lcsh:R Infant Newborn Infant Actin cytoskeleton medicine.disease Actins Cell biology Phenotype Membrane protein Child Preschool Oncology/Pediatric Oncology Female lcsh:Q Cell Adhesion Molecules Research Article Protein Binding |
| Zdroj: | PLoS ONE, Vol 3, Iss 11, p e3629 (2008) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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)/alpha-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 reported for some types of transfected cells. The observed ICAM-2-mediated suppression of metastatic phenotype is a novel function for this protein, and the interaction of ICAM-2/alpha-actinin/actin represents the first complete membrane-linker protein-actin linkage to impact tumor cell motility in vitro and metastatic potential in an in vivo model. Current work focuses on identifying specific protein domains critical to the regulation of neuroblastoma cell motility and metastasis and on determining if these domains represent exploitable therapeutic targets. |
| Databáze: | OpenAIRE |
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