Differential expression of perlecan receptors, α-dystroglycan and integrin ß1, before and after invasion of oral squamous cell carcinoma.

ABSTRACT

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 α-dystroglycan and integrin ß1 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, α-dystroglycan, integrin ß1, and Ki-67. In addition, α-dystroglycan mRNA signals were localized by in situ hybridization. RESULTS: In normal epithelia, α-dystroglycan and integrin ß1 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, α-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, α-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 ß1+ and Ki-67+ cells only to the periphery of SCC foci. α-Dystroglycan mRNA signals were basically identical to the α-dystroglycan protein localizations. CONCLUSION: The findings suggest that α-dystroglycan and integrin ß1 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.