Deregulation of E-cadherin by human papillomavirus is not confined to high-risk, cancer-causing types.
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.
Leong
C-M
CM
Department of Microbiology and Immunology and Pathology, University of Otago, PO Box 56, Dunedin, New Zealand.
Doorbar
J
J
Nindl
I
I
Yoon
H-S
HS
Hibma
M H
MH
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
D015820:Cadherins