Differential expression of perlecan receptors, α-dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma

OBJECTIVES: The deposition of perlecan, a heparan sulfate proteoglycan, is enhanced within oral carcinoma in situ (CIS) foci, while it dynamically switches from CIS foci to the stromal space in squamous cell carcinoma (SCC). Because alpha-dystroglycan and integrin beta 1 have been identified as two of the perlecan receptors, we wanted to determine their differential distributions before and after invasion of oral SCC. METHODS: Eighty-two surgical tissue specimens of oral SCC containing different precancerous stages were examined by immunohistochemistry for perlecan, alpha-dystroglycan, integrin beta 1, and Ki-67. In addition, alpha-dystroglycan mRNA signals were localized by in situ hybridization. RESULTS: In normal epithelia, alpha-dystroglycan and integrin beta 1 were localized on the cell membrane of basal cells, while perlecan was faintly present in the intercellular spaces of parabasal cells. In epithelial dysplasia and CIS, alpha-dystroglycan and perlecan were well co-localized in the epithelial layer, especially in its lower half, and this co-localization was mostly overlapped with Ki-67-positive (+) cell zones. However, in SCC, alpha-dystroglycan was localized neither within carcinoma cell nests nor in the stroma, while perlecan disappeared from SCC foci but emerged in the stromal space, leaving integrin beta 1+ and Ki-67+ cells only to the periphery of SCC foci. alpha-Dystroglycan mRNA signals were basically identical to the alpha-dystroglycan protein localizations. CONCLUSION: The findings suggest that alpha-dystroglycan and integrin beta 1 act as perlecan receptors in oral precancerous lesions prior to invasion, and that the perlecan signals via the two different receptors function in cellular differentiation and proliferation of CIS cells, respectively. J Oral Pathol Med (2010) 40: 552-559