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Neural cell adhesion molecule (NCAM) isoform expression is associated with neuroblastoma differentiation status
Author(s) -
Winter Cynthia,
Pawel Bruce,
Seiser Eric,
Zhao Huaqing,
Raabe Eric,
Wang Qun,
Judkins Alex R.,
Attiyeh Edward,
Maris John M.
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21475
Subject(s) - neural cell adhesion molecule , neuroblastoma , gene isoform , immunohistochemistry , microbiology and biotechnology , cell adhesion molecule , biology , western blot , neuroblast , cell adhesion , messenger rna , immunoglobulin superfamily , cancer research , pathology , cell culture , cell , medicine , gene , immunology , genetics , neurogenesis
Abstract Background NCAM is a member of the immunoglobulin superfamily of cell adhesion molecules. While highly expressed on neuroblastoma cells, the relative contribution of the three major NCAM isoforms (120, 140, and 180 kDa) to neuroblastoma biology has not been investigated. Methods NCAM protein expression was measured in a neuroblastic tumor tissue microarray (N = 185) by immunohistochemistry. Relative expression of NCAM mRNA isoforms was measured in a panel of 24 human neuroblastomas and compared to fetal and adult human brain using real‐time quantitative PCR and Western blot analysis. Associations with clinical and tumor biological co‐variates were performed. Results NCAM protein was detected on all neuroblastic tumors and was highly expressed in all but 7/167 cases. The mRNA species predicted to encode the 120 kDa protein species was the most abundant isoform in adult brain, ganglioneuromas and ganglioneuroblastomas ( P = 0.0007), but the mRNA predicted to encode the 180 kDa species was predominant in neuroblastomas ( P = 0.043). Microdissected ganglion and neuroblast cells from human primary tumors confirmed these findings. Conclusion Ganglioneuromas and ganglioneuroblastomas express the adhesive 120 kDa NCAM isoform, while neuroblastomas preferentially express the 180 kDa isoform classically involved in cell motility. These data suggest a mechanism for the enhanced metastatic potential of undifferentiated neuroblastomas. Pediatr Blood Cancer 2008;51:10–16. © 2008 Wiley‐Liss, Inc.