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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
NF-κ B-dependent upregulation of ICAM-1 by HPV16-E6/E7 facilitates NK cell/target cell interaction
International Journal of Cancer, Volume 128, No. 5, Year 2011
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Description
NK cell recognition of tumor cells is mediated by a delicate balance of signals received by MHC class I-binding inhibitory NK cell receptors and activating NK cell receptors, which mainly bind to virus-, stress- or tumor-induced ligands. In addition, adhesion molecules such as the intercellular adhesion molecule-1 (ICAM-1) and its receptors, the lymphocyte function-associated antigen-1 (LFA-1) and Mac-1, are crucial for immune synapse formation and NK cell-mediated killing. In this study, we show that expression of the adhesion molecule ICAM-1 was rapidly induced by E6 and -E7 oncoproteins of HPV16, -18, -5 and -8, but not of HPV38 and -6 in primary human keratinocytes after retroviral transduction. ICAM-1 was upregulated in E6E7-expressing keratinocytes both at mRNA and protein levels. The observed ICAM-1 upregulation in HPV16-E6E7-expressing keratinocytes was partially dependent on activation of the NF-κB pathway. Importantly, the upregulated ICAM-1 expression in HPV16-E6E7-expressing keratinocytes led to enhanced conjugate formation with NK cells. We previously showed that HPV16-positive cervical carcinomas frequently express low levels of inhibitory NK cell ligands and high levels of activating NK cell ligands. Moreover, levels of the adhesion molecule ICAM-1 are enhanced by HPV16-E6/E7. Therefore, strategies that aim at harnessing NK cells might be beneficial for the treatment of cervical carcinoma. © 2010 UICC.
Authors & Co-Authors
Textor, Sonja
Germany, Heidelberg
German Cancer Research Center
Accardi, Rosita
France, Lyon
Centre International de Recherche Sur le Cancer
Havlova, Tereza
Germany, Heidelberg
German Cancer Research Center
Hussain, Ishraq
India, Srinagar
Sher-e-kashmir University of Agricultural Sciences and Technology of Kashmir
Sylla, Bakary Sidiki
France, Lyon
Centre International de Recherche Sur le Cancer
Gissmann, Lutz Martin
Germany, Heidelberg
German Cancer Research Center
Saudi Arabia, Riyadh
King Saud University
Cerwenka, Adelheid
Germany, Heidelberg
German Cancer Research Center
Statistics
Citations: 19
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1002/ijc.25442
ISSN:
00207136
e-ISSN:
10970215
Research Areas
Cancer