title: Deregulation of E-cadherin by human papillomavirus is not confined to high-risk, cancer-causing types.
abstract: BACKGROUND
  E-cadherin is a tumour suppressor protein, which is normally expressed on keratinocytes and antigen-presenting Langerhans cells (LCs) in the epidermis. We have previously shown that E-cadherin is lost from tissues infected with the high-risk cancer-causing human papillomavirus (HPV) type 16.
  
  
  OBJECTIVE
  To test if E-cadherin dysregulation is associated with the cancer risk of the infecting HPV and to establish if it is conserved among HPVs in the α, β, γ and μ genera.
  
  
  METHODS
  Forty-seven lesions infected with low- or high-risk HPV types spanning four HPV genera were stained for E-cadherin, P-cadherin and CD1a to detect LCs.
  
  
  RESULTS
  Surface E-cadherin was reduced in tissues infected with members of the α4, α7 and α9 species and the γ and μ genera but was equivalent to normal epidermis in the β only-infected lesions tested and patchy in α10-infected tissues. There was a direct relationship between atypical E-cadherin expression and a significant reduction in LCs. Expression of P-cadherin, a protein that is increased in the E-cadherin constitutive knockout mouse, was increased in lesions with reduced E-cadherin.
  
  
  CONCLUSIONS
  These data show that E-cadherin dysregulation by HPV is widely conserved across the majority of HPV genera. E-cadherin expression was reduced or lost in epidermis irrespective of the cancer risk of the infecting HPV type or the ability of the virus to degrade retinoblastoma protein or p53. A correlation between dysregulated E-cadherin and reduced numbers of LCs supports viral regulation of surface E-cadherin contributing to viral evasion of the host immune system.
authors.affiliation: Department of Microbiology and Immunology and Pathology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: C-M
authors.initials: CM
authors.lastname: Leong
authors.forename: J
authors.initials: J
authors.lastname: Doorbar
authors.forename: I
authors.initials: I
authors.lastname: Nindl
authors.forename: H-S
authors.initials: HS
authors.lastname: Yoon
authors.forename: M H
authors.initials: MH
authors.lastname: Hibma
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D003218:Condylomata Acuminata / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000473:pathology; D008297:Male; D027383:Papillomaviridae / Q000145:classification; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology
chemical_list: D015820:Cadherins