Caberg Jean-Hubert D, Hubert Pascale M, Begon Dominique Y, Herfs Michael F, Roncarati Patrick J, Boniver Jacques J, Delvenne Philippe O
Department of Pathology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer, B23, University of Liege, Centre Hospitalier Universitaire Sart Tilman, 4000 Liege, Belgium.
Carcinogenesis. 2008 Jul;29(7):1441-7. doi: 10.1093/carcin/bgn145. Epub 2008 Jun 19.
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The persistence or progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most squamous intra-epithelial lesions show quantitative and functional alterations of Langerhans cells (LCs). Moreover, E-cadherin-dependent adhesion of LC to keratinocytes (KCs) is defective in cervical HPV16-associated (pre)neoplastic lesions. The possible role of viral oncoprotein E7 in the reduced levels of cell surface E-cadherin was investigated by silencing HPV16 E7 by RNA interference (siRNA). This treatment induced an increased cell surface E-cadherin expression in HPV16-positive KC and a significant adhesion of LC to these squamous cells. The E-cadherin re-expression following HPV16 E7 silencing was associated with increased detection levels of retinoblastoma protein and the activating protein (AP)-2alpha transcription factor. These data suggest that HPV16 E7-induced alterations of LC/KC adhesion may play a role in the defective immune response during cervical carcinogenesis.
人乳头瘤病毒（HPV）感染，尤其是16型，与子宫颈癌存在因果关联。宫颈病变的持续或进展表明病毒抗原未充分呈递给免疫系统。大多数鳞状上皮内病变显示朗格汉斯细胞（LC）存在数量和功能改变，这一观察结果进一步支持了该假说。此外，在宫颈HPV16相关的（癌前）病变中，LC与角质形成细胞（KC）之间依赖E-钙黏蛋白的黏附存在缺陷。通过RNA干扰（siRNA）使HPV16 E7沉默，研究了病毒癌蛋白E7在细胞表面E-钙黏蛋白水平降低中可能发挥的作用。该处理导致HPV16阳性KC中细胞表面E-钙黏蛋白表达增加，且LC与这些鳞状细胞发生显著黏附。HPV16 E7沉默后E-钙黏蛋白的重新表达与视网膜母细胞瘤蛋白和激活蛋白（AP）-2α转录因子检测水平的增加相关。这些数据表明，HPV16 E7诱导的LC/KC黏附改变可能在宫颈癌发生过程中的免疫反应缺陷中发挥作用。
