%0 Journal Article
%T Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells
%A Luc Friboulet
%A Claire Gourzones
%A Sai Tsao
%A Yannis Morel
%A Carine Paturel
%A St¨¦phane T¨¦mam
%A Catherine Uzan
%A Pierre Busson
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-327
%X This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types.We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines.Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas.Toll-like receptor 3, a membrane receptor of double strand RNAs, is a major effector of the immune response against viral pathogens at the cellular and systemic level. It is involved in early activation of NK and dendritic cells. It is also expressed in a wide range of non-immune cells where it plays a key role in the induction of interferon response [1]. TLR3 is frequently expressed by malignant cells of various types and there are several observations suggesting that it can be targeted for therapeutic purpose [2,3]. At least one clinical trial has shown a therapeutic benefit for breast carcinoma patients treated with the synthetic TLR3 agonist poly(A/U) [4]. On the other hand, several in vitro studies have reported apoptosis induction in malignant cells treated with the synthetic TLR3-agonist, poly(I:C). However, these results were obtained using very high concentrations of this agent in the range of 10 to 100 ¦̀g/ml [5-9]. Such concentrations are probably incompatible with doses of synthetic ligands acceptable for patient treatment. One of our
%U http://www.biomedcentral.com/1471-2407/10/327