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


CONCLUSIONS
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.
Winter
Cynthia
C
Division of Oncology, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Pawel
Bruce
B
Seiser
Eric
E
Zhao
Huaqing
H
Raabe
Eric
E
Wang
Qun
Q
Judkins
Alex R
AR
Attiyeh
Edward
E
Maris
John M
JM
D000328:Adult; D005333:Fetus; D018305:Ganglioneuroblastoma / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019006:Neural Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D009447:Neuroblastoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D012333:RNA, Messenger