Toll-like receptor 3 expressed by melanoma cells as a target for therapy?
Details
Serval ID
serval:BIB_E05E8324B0E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Toll-like receptor 3 expressed by melanoma cells as a target for therapy?
Journal
Clinical cancer research
ISSN
1078-0432
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
13
Number
15 Pt 1
Pages
4565-4574
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
PURPOSE: The immunomodulatory properties of Toll-like receptors (TLR) agonists have inspired their use as experimental adjuvants for vaccination of cancer patients. However, it is now well recognized that TLR expression is not restricted to immune cells but can also be found in many cell types, including those giving rise to tumors. It is therefore mandatory to explore the potential effects of TLR triggering directly on tumor cells. EXPERIMENTAL DESIGN: In the present work, we have investigated TLR3 protein expression in melanoma cell lines derived from patients, and analyzed the effects of TLR3 agonists on tumor cell survival. Moreover, we used RNA interference to stably knock down TLR3 expression and study the involvement of this receptor in dsRNA-induced effects on melanoma cells viability. RESULTS: Human melanoma cells can express functional TLR3 protein. Interestingly, the engagement of the receptor by TLR3 agonists can directly inhibit cell proliferation and induce tumor cell death when combined to treatment with either type I IFN or protein synthesis inhibitors. These effects were shown by RNA interference to be largely dependent on TLR3. Moreover, TLR3-mediated cell death involves the activation of caspases and engages both extrinsic and intrinsic apoptotic pathways. CONCLUSION: TLR3 protein can be expressed in human melanoma cells, where it can deliver proapoptotic and antiproliferative signaling. Altogether, these results suggest that TLR3 agonists represent very promising adjuvants for cancer vaccines not only based on their well-described immunostimulatory properties, but also due to their newly identified cytostatic and cytotoxic effects directly on tumor cells.
Keywords
Apoptosis/immunology, Caspases/metabolism, Cell Proliferation, Humans, Immunoprecipitation, Interferon-alpha/pharmacology, Lentivirus/genetics, Melanoma/metabolism, Melanoma/pathology, Poly I-C/pharmacology, RNA Interference, Skin Neoplasms/metabolism, Skin Neoplasms/pathology, Toll-Like Receptor 3/agonists, Toll-Like Receptor 3/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:28
Last modification date
20/08/2019 17:04