Reference : Transforming growth factor-beta1-mediated Slug and Snail transcription factor up-regulat...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
Human health sciences : Oncology
http://hdl.handle.net/2268/10032
Transforming growth factor-beta1-mediated Slug and Snail transcription factor up-regulation reduces the density of Langerhans cells in epithelial metaplasia by affecting E-cadherin expression
English
Herfs, Michael mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Hubert, Pascale mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Kholod, Natalia [ > > ]
Caberg, Jean-Hubert mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Gilles, Christine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Berx, Geert [ > > ]
Savagner, Pierre [ > > ]
Boniver, Jacques mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
Delvenne, Philippe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
May-2008
American Journal of Pathology
American Society for Investigative Pathology
172
5
1391-402
Yes (verified by ORBi)
International
0002-9440
1525-2191
Bethesda
MD
[en] Metaplasia ; TGF-beta ; carcinogenesis
[fr] Langerhans cells ; Snail Slug ; E-cadherin
[en] Epithelial metaplasia (EpM) is an acquired tissue abnormality resulting from the transformation of epithelium into another tissue with a different structure and function. This adaptative process is associated with an increased frequency of (pre)cancerous lesions. We propose that EpM is involved in cancer development by altering the expression of adhesion molecules important for cell-mediated antitumor immunity. Langerhans cells (LCs) are intraepithelial dendritic cells that initiate immune responses against viral or tumor antigens on both skin and mucosal surfaces. In the present study, we showed by immunohistology that the density of CD1a LCs is reduced in EpM of the uterine cervix compared with native squamous epithelium and that the low number of LCs observed in EpM correlates with the down-regulation of cell-surface E-cadherin. We also demonstrated that transforming growth factor- 1 is not only overexpressed in metaplastic tissues but also reduces E-cadherin expression in keratinocytes in vitro by inducing the promoter activity of Slug and Snail transcription factors. Finally, we showed that in vitro-generated LCs adhere poorly to keratinocytes transfected with either Slug or Snail DNA. These data suggest that transforming growth factor- 1 indirectly reduces antigenpresenting cell density in EpM by affecting E-cadherin expression, which might explain the increased susceptibility of abnormal tissue differentiation to the development of cancer by the establishment of local immunodeficiency responsible for EpM tumorigenesis.
Researchers
http://hdl.handle.net/2268/10032
10.2353/ajpath.2008.071004

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