Alterations of collagen XVII expression during transformation of oral epithelium to dysplasia and carcinoma.
Collagen XVII (BP180) is a hemidesmosomal transmembrane component that has been hypothesized to participate in keratinocyte adhesion and motility. Using immunohistochemical (IHC) and in situ hybridization (ISH) methods, we showed downregulation of collagen XVII in basal cells in mild dysplasias and upregulation in suprabasal keratinocytes in moderate and severe dysplasias as well as in the central cells of grade II and III squamous cell carcinomas (SCCs). Overexpression of collagen XVII was found at the invasive front of the tumors. Collagen XVII and its cleaved ectodomain were characterized from culture extracts and precipitates of oral keratinocytes, tongue carcinoma cells, and tumor tissue extract. Malignant cell lines exhibited increased collagen XVII expression in immunoblotting analysis. In oral keratinocytes, collagen XVII gene expression was significantly induced by PMA but not by the inflammatory cytokines TGF-beta1, TNF-alpha, EGF, IL-1beta, and IL-6. These results indicate altered expression of collagen XVII at different stages of carcinogenesis and suggest a correlation between overexpression of collagen XVII and tumor progression. The reduced collagen XVII expression at the early step of carcinogenesis may reflect disturbed keratinocyte adhesion to the basement membrane.
Parikka
Mataleena
M
Department of Diagnostic and Oral Medicine, University of Oulu, and Oulu University Hospital, 90014 Oulu, Finland.
Kainulainen
Tiina
T
Tasanen
Kaisa
K
Väänänen
Anu
A
Bruckner-Tuderman
Leena
L
Salo
Tuula
T
D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C486268:DST protein, human