ICAM-2 confers a non-metastatic phenotype in neuroblastoma cells by interaction with α-actinin.

摘要: Progressive metastatic disease is a major cause of mortality for patients diagnosed with multiple types solid tumors. One the long-term goals our laboratory to identify  molecular interactions that regulate metastasis, as basis developing agents inhibit this process. Toward goal, we recently demonstrated intercellular adhesion molecule-2 (ICAM-2) converted neuroblastoma (NB) cells from non-metastatic phenotype, previously unknown function ICAM-2. Interestingly, ICAM-2 suppressed but not tumorigenic potential in preclinical models, supporting novel mechanism regulating metastasis. We hypothesized effects on NB cell phenotype depend interaction cytoskeletal linker protein α-actinin. The goal study presented here was evaluate impact α-actinin binding of NB tumor cells. used silico approaches examine likelihood cytoplasmic domain binds directly then expressed variants mutated α-actinin-binding domains, and compared each variant adhesion, migration, anchorage-independent growth, co-precipitation production localized disseminated tumors vivo. vitro vivo characteristics expressing modified domains differed wild type (WT) also no detectable Like WT protein, inhibited migration colony growth vitro. However, unlike did completely suppress development data suggest presence α-actinin-dependent α-actinin-independent mechanisms, indicate critical conferring an ICAM-2-mediated