Aberrant expression of β-dystroglycan may be due to processing by matrix metalloproteinases-2 and -9 in oral squamous cell carcinoma

SummaryDystroglycan (DG), a non-integrin adhesion molecule, is formed by two subunits, α- and β-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 β-DG remains largely unknown. In this study, we investigated the correlation of β-DG degradation with invasiveness in oral squamous cell carcinoma (OSCC) and its possible processing by matrix metalloproteinases (MMP). Immunohistochemical staining was used to assess β-DG expression in 60 cases of OSCC. The effects of the MMP inhibitor 1,10-phenanthroline on tumour cell invasion and β-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 β-DG by MMP. The α- and β-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 30 kDa fragment of β-dystroglycan (β-DG30) in addition to β-DG itself. β-DG degradation was almost abolished using 1,10-phenanthroline and there was a significant decrease in tumor cell invasion. The N-terminal sequence of β-DG30 was detected as Ile-Asn-Thr-Asn, or Ile-Val-Thr-Gln. We conclude that β-DG degradation may play a role both in OSCC invasion and metastasis. MMP activity seems to be one mechanism for β-DG processing into β-DG30.