Expression of Epstein-Barr virus latent membrane proteins leads to changes in keratinocyte cell adhesion.
Epstein-Barr virus (EBV) has 3 latent membrane proteins (LMPs)--LMP1, LMP2a, and LMP2b--which are expressed in nasopharyngeal carcinoma. Using keratinocyte cell lines expressing LMP2a and LMP2b and coexpressing LMP1/LMP2a, we grew organotypic raft cultures to analyze changes in morphology and expression of the cell adhesion molecule ICAM-1; alpha2, alpha3, alpha5, beta1, and alpha6beta4 integrins; laminin 5; E-cadherin; and desmoplakin. Cells expressing LMP2a or LMP2b were defective in their ability to mature and progress through normal squamous stratification when compared to the parental cell lines. Cells coexpressing LMP1/LMP2a additionally demonstrated "pseudoinvasion" into the raft dermal equivalent. There was a consistent and dramatic up-regulation in the suprabasal expression of laminin 5 and alpha6beta4 and beta1 integrins in the LMP-expressing cell lines. ICAM-1, not expressed in the control cell lines, was up-regulated in the LMP-expressing cell lines. Expression of alpha3 and alpha5 integrins was also up-regulated in the LMP-expressing cell lines, while alpha2 demonstrated a loss of the normal basal layer expression. E-cadherin and desmoplakin expression patterns were essentially unchanged. We conclude that LMP2a and LMP2b singly, and LMP1/LMP2a coexpressed, are capable of altering keratinocyte cell adhesion molecule expression consistent with nasopharyngeal carcinoma.
Farwell
D G
DG
Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle 98195, USA.
McDougall
J K
JK
Coltrera
M D
MD
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D002448:Cell Adhesion; D015870:Gene Expression / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000502:physiology* / Q000821:virology; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000821:virology; D011956:Receptors, Cell Surface / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011956:Receptors, Cell Surface; D014763:Viral Matrix Proteins