Neural cell adhesion molecule (NCAM) isoform expression is associated with neuroblastoma differentiation status

Cynthia Winter, Bruce Pawel, Eric Seiser, Huaqing Zhao, Eric Raabe, Qun Wang, Alex R. Judkins, Edward Attiyeh, John M. Maris

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10-16
Number of pages7
JournalPediatric Blood and Cancer
Volume51
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Ganglioneuroblastoma
  • Ganglioneuroma
  • Isoform
  • Neural cell adhesion molecule (NCAM)
  • Neuroblastoma
  • Tissue microarray

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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