Aberrant expression of beta-dystroglycan may be due to processing by matrix metalloproteinases-2 and -9 in oral squamous cell carcinoma.
Dystroglycan (DG), a non-integrin adhesion molecule, is formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. The exact proteolytic processing of beta-DG remains largely unknown. In this study, we investigated the correlation of beta-DG degradation with invasiveness in oral squamous cell carcinoma (OSCC) and its possible processing by matrix metalloproteinases (MMP). Immunohistochemical staining was used to assess beta-DG expression in 60 cases of OSCC. The effects of the MMP inhibitor 1,10-phenanthroline on tumour cell invasion and beta-DG degradation were investigated using in vitro invasion assays and immunoblot analysis. Co-immunoprecipitation and N-terminal sequencing were performed to determine the possible cleavage site of beta-DG by MMP. The alpha- and beta-DG expression was reduced or lost in OSCC. In four cell lines studied (SCC-4, SCC-9, SCC-15 and SCC-25), Western blot revealed a 30kDa fragment of beta-dystroglycan (beta-DG30) in addition to beta-DG itself. beta-DG degradation was almost abolished using 1,10-phenanthroline and there was a significant decrease in tumor cell invasion. The N-terminal sequence of beta-DG30 was detected as Ile-Asn-Thr-Asn, or Ile-Val-Thr-Gln. We conclude that beta-DG degradation may play a role both in OSCC invasion and metastasis. MMP activity seems to be one mechanism for beta-DG processing into beta-DG30.
Shang
Zheng Jun
ZJ
Key laboratory for Oral Biomedical Engineering, Ministry of Education, Wuhan University, 237 Luoyu Road, Wuhan 430079, China. shangzhengjun@hotmail.com
Ethunandan
Madanagopalan
M
Górecki
Dariusz C
DC
Brennan
Peter A
PA
D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D049030:Dystroglycans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9