Neuroblastoma: Role of Activated Leukocyte Cell Adhesion Molecule

Abstract

Neuroblastoma is a rare sympathetic nervous system neoplasia with a broad spectrum of clinical presentations. Prognosis depends on age, stage, genetic and histological features. However, in spite of favorable prognostic factors, the event-free survival of some neuroblastoma patients with localized disease may be poor. Since the Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), involved in nervous system development and neuritis extension, has been linked to tumor progression and metastasis in several tumor types, we studied its expression in neuroblastoma cell lines and primary tumors from patients with localized neuroblastoma. Neuroblastoma cell lines display various levels of ALCAM surface expression, which can be dynamically regulated by metalloprotease-mediated shedding. More importantly, ALCAM is expressed also in neuroblastoma primary tumors and diverse patterns of subcellular localization can be observed. In patients with localized disease and favorable prognostic factors, high levels of ALCAM membrane expression, together with low expression in the cytoplasm and neuropil area, were significantly associated with relapse, suggesting that high ALCAM membrane expression may represent a new negative prognostic factor in these patients. In conclusion, assessment of ALCAM subcellular localization may represent a useful tool to identify patients at high risk of relapse that could benefit from a more careful follow-up.