title: Differential expression of perlecan receptors, α-dystroglycan and integrin β1, before and after invasion of oral squamous cell carcinoma.
abstract: OBJECTIVE
  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 β1 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 β1, and Ki-67. In addition, α-dystroglycan mRNA signals were localized by in situ hybridization.
  
  
  RESULTS
  In normal epithelia, α-dystroglycan and integrin β1 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 β1+ and Ki-67+ cells only to the periphery of SCC foci. α-Dystroglycan mRNA signals were basically identical to the α-dystroglycan protein localizations.
  
  
  CONCLUSIONS
  The findings suggest that α-dystroglycan and integrin β1 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.
authors.affiliation: Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Ahsan
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Takanori
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Adeola
authors.initials: A
authors.lastname: Henry Ademola
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D002278:Carcinoma in Situ / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002462:Cell Membrane / Q000473:pathology; D049030:Dystroglycans / Q000032:analysis* / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005110:Extracellular Space / Q000737:chemistry; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis*; D006801:Humans; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000473:pathology
chemical_list: C483081:DAG1 protein, human; D019812:Heparan Sulfate Proteoglycans; D019012:Integrin beta1; D019394:Ki-67 Antigen; D012333:RNA, Messenger; C071927:perlecan; D049030:Dystroglycans