title: Differential expression of basement membrane collagen-IV alpha1 to alpha6 chains during oral carcinogenesis.
abstract: This study aimed to resolve if basement membrane (BM) collagen alpha chains undergo remodeling during oral carcinogenesis. Using immunohistochemistry and transmission electron microscopy, we found that BMs in oral epithelial dysplasias (OED: mild, n=10; moderate, n=10; severe, n=10) and carcinoma in situ (CIS) (n=10) differed from normal mucosa (n=6) and oral epithelial hyperplasia (n=5) in showing: (1) excessive lamina densa-like material ultrastructurally, and (2) stronger immunoexpression for alpha5(IV) than for alpha1(IV), alpha2(IV), and alpha6(IV) chains-findings that implicate these molecules' role as an adhesive template for the attachment and persistence of basal dysplastic cells. Incipient loss of BM integrity in CIS, where alpha5(IV)/alpha6(IV) chains were more frequently absent than alpha1(IV)/alpha2(IV) chains, suggests that alpha(IV) network disruption is crucial for progression of dysplastic cells into the extracellular compartment, marking transition into the invasive phase. In carcinomatous BM, the disappearance of alpha(IV) chains was more severe in poorly differentiated oral squamous cell carcinoma (OSCC) (n=10) than in well-differentiated OSCC (n=10). In all samples examined, alpha3(IV) and alpha4(IV) chains were absent. These findings taken together suggest that BM collagen-IV alpha chains undergo remodeling where selective increase and loss of these molecules are probably early and late events, respectively, during progression of oral dysplasia to cancer.
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama, 700-8525, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tamamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: Chong Huat
authors.initials: CH
authors.lastname: Siar
authors.forename: Naoki
authors.initials: N
authors.lastname: Katase
authors.forename: Ichiro
authors.initials: I
authors.lastname: Naito
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
mesh_terms: D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D024141:Collagen Type IV / Q000145:classification / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D046529:Microscopy, Electron, Transmission; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009092:Mucous Membrane / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D014408:Biomarkers, Tumor; D024141:Collagen Type IV