Abstract
Background. The neural cell adhesion molecule (NCAM) has numerous isoforms resulting from alternative
splicing of mRNA. The 3 major isoforms found in adult tissue are (1) a 120-kDa protein
that is linked to the plasma membrane by glycosylphosphatidylinositol; (2) a 140-kDa
form that has a transmembrane component and a cytoplasmic tail with unknown function;
and (3) a 180-kDa isoform that has an intracellular protein that binds the cytoskeleton.
NCAM is capable of homotypic binding and therefore plays a role in cell-cell adhesion
for cells expressing the 180-kDa isoform by anchoring groups of cells into epithelial
sheets. NCAM-180 is the isoform found in colonocytes, and loss of expression is associated
with clinically aggressive colon cancers. Methods. Western blotting and reverse transcriptase-polymerase chain reaction were used to
screen commercially available cell lines for NCAM-180 expression. For cell-line pairs
with differential NCAM-180 expression, exon analysis was performed with reverse transcriptase-polymerase
chain reaction to determine where the molecule was spliced, culminating in failed
expression. These results were confirmed with exon analysis in colon cancers harvested
at the time of laparotomy. Results. Analysis of a SW480 cell line (derived from a patient's primary colon cancer lesion)
revealed NCAM-180 expression, whereas no expression was found in the SW620 cell line
(derived from a metastatic lesion from the same patient). Exon analysis of NCAM mRNA
transcripts from SW620 revealed that the transcripts were truncated after exon 12.
This region correlates to an area between 2 fibronectin-III domains on the NCAM protein.
Conclusions. The most common site for NCAM alternative splicing is between the 2 fibronectin-III
domains corresponding to the border between exons 12 and 13 of the NCAM gene. Loss
of NCAM-180 expression in aggressive colon carcinoma results from a splice defect
in the same area, which may result in defective intracellular adhesion between colonocytes.
(Surgery 2001;130:834-43.)
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References
- General mechanisms of metastasis.Cancer. 1997; 80: 1529-1537
- Membrane proteases: roles in tissue remodeling and tumour invasion.Curr Opin Cell Biol. 1992; 4: 802-809
- Tumor cell surface determinants in host immunity against metastases.Semin Cancer Biol. 1991; 2: 179-188
- Cell motility in angiogenesis and tumor metastasis.Cancer Invest. 1990; 8: 669-671
- Cellular basis of site-specific tumor metastasis.N Engl J Med. 1990; 322: 605-612
- Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule.Cell. 1989; 57: 327-334
- NCAM: structural diversity, function and regulation of expression.Semin Cell Biol. 1992; 3: 189-197
- The distribution of the deleted in colon cancer (DCC) protein in human tissues.Cancer Res. 1995; 55: 5628-5631
- Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues.Cancer Res. 1994; 54: 4493-4501
- Topographic localization of the heparin-binding domain of the neural cell adhesion molecule N-CAM 1986.J Cell Biol. 1986; 103: 1739-1744
- Functional cooperation between the neural adhesion molecules L1 and N-CAM is carbohydrate dependent.J Cell Biol. 1990; 110: 209-218
- The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions.J Cell Biol. 1990; 110: 193-208
- Differences in the carbohydrate structures of neural cell-adhesion molecules from adult and embryonic chicken brains.J Biol Chem. 1982; 257: 11064-11069
- The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions.Science. 1988; 240: 53-57
- Characterization of cDNA clones defining variant forms of human neural cell adhesion molecule N-CAM.J Mol Neurosci. 1990; 2: 71-78
- The 180-kD component of the neural cell adhesion molecule N-CAM is involved in cell-cell contacts and cytoskeleton-membrane interactions.Cell Tissue Res. 1987; 250: 227-236
- Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors.Invasion Metastasis. 1998; 18: 271-284
- Expression of neural cell adhesion molecule-related sialoglycoprotein in small cell lung cancer and neuroblastoma cell lines H69 and CHP-212.Cancer Res. 1990; 50: 1102-1106
- Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma.Am J Surg. 1997; 174: 251-257
- Neural cell-to-cell adhesion and recognition.Curr Opin Cell Biol. 1989; 1: 898-904
- Multiple intron retention occurs in tumor cell CD44 mRNA processing.Am J Pathol. 1998; 153: 1221-1228
- Clinical implications of anomalous CD44 gene expression in neoplasia [In Process Citation].Front Biosci. 1998; 3: E89-E109
- Current status of CD44 variant isoforms as cancer diagnostic markers.Histopathology. 1998; 32: 1998
- Rapid analysis of distinctive CD44 RNA splicing preferences that characterize colonic tumors.Cancer Res. 1997; 57: 3140-3144
- Classification of human colorectal adenocarcinoma cell lines.Cancer Res. 1976; 36: 4562-4569
- One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice.J Natl Cancer Inst. 1977; 59: 221-226
- Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle-specific sequence in the extracellular domain.Cell. 1987; 50: 1119-1130
- The muscle specific domain of mouse N-CAM: structure and alternative splicing patterns.Nucleic Acids Res. 1991; 19: 4709-4716
- Four exons encode a 93-base-pair insert in three neural cell adhesion molecule mRNAs specific for chicken heart and skeletal muscle.Proc Natl Acad Sci U S A. 1988; 85: 9616-9620
- Differential exon usage involving an unusual splicing mechanism generates at least eight types of NCAM cDNA in mouse brain.EMBO J. 1989; 8: 385-392
- Alternative splicing generates a secreted form of N-CAM in muscle and brain.Cell. 1988; 55: 955-964
- Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31.Genomics. 1996; 35: 456-465
- Identification of the border between fibronectin type III homologous repeats 2 and 3 of the neural cell adhesion molecule L1 as a neurite outgrowth promoting and signal transducing domain.J Neurobiol. 1995; 28: 297-312
- Neural cell recognition molecule F11: homology with fibronectin type III and immunoglobulin type C domains.Neuron. 1989; 2: 1351-1361
- Growth cone guidance in insects: fasciclin II is a member of the immunoglobulin superfamily.Science. 1988; 242: 700-708
- Evolution of the neural immunoglobin supergene family and functional studies of one of its members [thesis/dissertation].California Institute of Technology, 1997
- NCAM-fibronectin-type-III-domain substrata with and without a six-amino-acid-long proline-rich insert increase the dendritic and axonal arborization of spinal motoneurons.J Neurosci Res. 1997; 48: 112-121
- Crystal structure of tandem type III fibronectin domains from Drosophila neuroglian at 2.0 A.Neuron. 1994; 12: 717-731
Article info
Publication history
Accepted:
April 6,
2001
Footnotes
*Reprint requests: Edward H. Livingston, MD, Chief, Department of Surgery (10H2), VA Greater Los Angeles Health Care System, 11301 Wilshire Blvd, Los Angeles, CA 90073.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
