Aberrant expression, processing and degradation of dystroglycan in squamous cell carcinomas.
The alpha- and beta- dystroglycan (DG) proteins are involved in epithelial cell development, formation of the basement membrane and maintenance of tissue integrity. Recently, specific changes in the expression patterns of DGs have been described in some cancers. We studied the expression and localisation of alpha- and beta-DG using Western blotting, immunohistochemistry and reverse transcriptase-polymerase chain reaction analyses in samples of normal oral mucosa, oral squamous cell carcinoma (SCC) and cancer cell lines. The alpha- and beta-DG were localised in the basal layers of normal oral mucosa.However, beta-DG expression in cancer tissues showed evidence of aberrant expression, processing and degradation. alpha-DG was altered in all oral cancer samples and cell lines, despite the persistent presence of DG mRNA in cancer cells. Using matrix metalloproteinase (MMP) inhibitors, we determined that beta-DG degradation in carcinoma cell lines can be mediated by MMPs but this process is highly variable, even in cells from the same cancer type. Considering the multifaceted role of DG in epithelial development, it appears that the role of DG degradation in cancer growth and spread, although currently poorly understood, may be important.
Jing
Jie
J
School of Pharmacy and Biomedical Sciences, Institute of Biomedical and Biomolecular Sciences, Molecular Medicine Group, University of Portsmouth, St. Michael's Building, White Swan Road, PO1 2DT, UK.
Lien
Chun Fu
CF
Sharma
Sanjay
S
Rice
Jill
J
Brennan
Peter A
PA
Górecki
Dariusz C
DC
D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049030:Dystroglycans