title: Reduced glycosylation of α-dystroglycans on carcinoma cells contributes to formation of highly infiltrative histological patterns in prostate cancer.
abstract: BACKGROUND
  α-Dystroglycan (DG) carries glycan chains that bind to laminin and thus function in homeostasis of not only skeletal muscle but also of various epithelial cells. Loss of glycosylation has been suggested to play important roles in tumor development, particularly in detachment and migration of carcinoma cells. We previously reported that glycosylation of α-DG, but not levels of α-DG core protein itself, is reduced in prostate carcinoma. In this study, we investigate the association between reduction of laminin-binding glycans on α-DG and the degree of tumor cell differentiation and/or infiltrative properties, as assessed by the Gleason grading system.
  
  
  METHODS
  Immunohistochemical analysis of 146 biopsy specimens of prostate adenocarcinoma with various Gleason scores was carried out employing IIH6 and 6C1 antibodies, which recognize laminin-binding glycans on α-DG and α-DG core proteins, respectively. Double immunofluorescence staining was performed to evaluate colocalization of α-DG and laminin, and to determine which types of epithelial cells express laminin-binding glycans on α-DG.
  
  
  RESULTS
  Reduction of α-DG glycosylation, rather than loss of α-DG core protein, was correlated with higher Gleason patterns. Reduction was most conspicuous at the interface between carcinoma cells and the basement membrane. In addition, in non-neoplastic prostate glands, laminin-binding glycans were expressed predominantly on the basolateral surface of basal cells.
  
  
  CONCLUSIONS
  Reduced expression of laminin-binding glycans on α-DG may contribute to formation of highly infiltrative behavior of prostate carcinoma cells. Substantial reduction of laminin-binding glycans in carcinoma tissue could be partly ascribed to disappearance of pre-existing basal cells.
authors.affiliation: Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shimojo
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kamigaito
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Shimojo
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D018267:Carcinoma, Acinar Cell / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D049030:Dystroglycans / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C483081:DAG1 protein, human; D007797:Laminin; D049030:Dystroglycans