Abstract

Background: The Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD), involved in nervous system development, has been linked to tumor progression and metastasis in several tumors. No information is available on ALCAM expression in neuroblastoma, a childhood neoplasia originating from the sympathetic nervous system.Methods: ALCAM expression was analysed by immunofluorescence and immunohistochemistry on differentiated neuroblastoma cell lines and on archival specimens of stroma-poor, not MYCN amplified, resectable neuroblastoma tumors, respectively.Results: ALCAM is variously expressed in neuroblastoma cell lines, is shed by metalloproteases and is cleaved by ADAM17/TACE in vitro. ALCAM is expressed in neuroblastoma primary tumors with diverse patterns of subcellular localization and is highly expressed in the neuropil area in a subgroup of cases. Tumor specimens showing high expression of ALCAM at the membrane of the neuroblast body or low levels in the neuropil area are associated with relapse (P = 0.044 and P < 0.0001, respectively). In vitro differentiated neuroblastoma cells show strong ALCAM expression on neurites, suggesting that ALCAM expression in the neuropil is related to a differentiated phenotype.Conclusions: Assessment of ALCAM localization by immunohistochemistry may help to identify patients who, in the absence of negative prognostic factors, are at risk of relapse and require a more careful follow-up.

Highlights

  • Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a member of the Immunoglobulin gene superfamily, which mediates cell–cell clustering through homophilic (ALCAM–ALCAM) and heterophilic (ALCAM-CD6) interactions

  • By mean of an anti-ALCAM recombinant single chain antibody, we previously showed that ALCAM is expressed at the surface of epithelial ovarian cancer (EOC) cells, can be internalized following soluble ligand engagement [21] and is released in a soluble form by a disintegrin and metalloprotease (ADAM)17/TACEdependent mechanism [24]

  • A panel of 13 human neuroblastoma cell lines was analysed for cell surface ALCAM expression by flow cytometry

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Summary

Introduction

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a member of the Immunoglobulin gene superfamily, which mediates cell–cell clustering through homophilic (ALCAM–ALCAM) and heterophilic (ALCAM-CD6) interactions (reviewed in Swart [30]). In adult tissues ALCAM expression is limited to subsets of cells, whereas in several human tumors, including melanoma, prostate, breast, bladder and colorectal cancer, alterations in expression of ALCAM have been reported ALCAM role in tumor progression and metastasis has been well documented in other tumors. High levels of ALCAM membrane expression correlate with the vertical growth phase of tumor progression [33]. The Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), involved in nervous system development, has been linked to tumor progression and metastasis in several tumors. No information is available on ALCAM expression in neuroblastoma, a childhood neoplasia originating from the sympathetic nervous system

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