Expression of alternative isoforms of the neural cell adhesion molecule (NCAM) on normal brain and a variety of brain tumours.
A panel of monoclonal antibodies, including a reagent designated ERIC-1, have been characterized as binding to the human neural cell adhesion molecule (NCAM). These monoclonal antibodies bind in a relatively uniform manner to a variety of normal and neoplastic tissues arising from the neuroectoderm. However, multiple forms of the protein are known to arise from the differential splicing of exons within the NCAM gene located on chromosome 11 at q23. On human adult brain, four isoforms of 180, 170, 145 and 120 kDa have been identified. Here, we report the identification of another NCAM isoform of 95 kDa that is apparent on tissues following either N-glycanase or neuraminidase treatment to remove carbohydrate and sialic acid residues from the molecule respectively. NCAM expression is further complicated by differential post-translational modification of the molecule which is developmentally regulated. In general, fetal NCAM is more heavily polysialylated than the adult forms of the molecule. Human fetal brain has been shown to express the heavily sialylated embryonic form of NCAM, but following neuraminidase digestion, a similar pattern of NCAM expression is seen to that in adult brain. A variety of human brain tumours examined also show different patterns of NCAM expression, despite their uniform staining with monoclonal antibodies. The significance of these observations for designing new molecular and immunological approaches to the diagnosis of a variety of primary tumours is reviewed.
Frost
G
G
Imperial Cancer Research Fund, Paediatric and Neuro-oncology Group, Frenchay Hospital, Bristol.
Patel
K
K
Bourne
S
S
Coakham
H B
HB
Kemshead
J T
JT
D000328:Adult; D000581:Amidohydrolases; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis*; D005333:Fetus / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D006801:Humans; D009439:Neuraminidase; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D009439:Neuraminidase; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase