| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Cancer Research UK Institute for Cancer Studies and Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, and
City Hospital National Health Service Trust, Birmingham, United Kingdom;
Section of Infection and Immunity, University of Wales College of Medicine, Cardiff, United Kingdom; and
Department of Clinical Chemistry, Lund University, The Wallenberg Laboratory, University Hospital, Malmo, Sweden
In this study, we describe the expression and function of CD40, a TNF receptor family member, in cervical carcinomas. CD40 was present at very low levels in normal cervical epithelium but was overexpressed in human papillomavirus-infected lesions and advanced squamous carcinomas of the cervix. The stimulation of CD40-positive cervical carcinoma cell lines with soluble CD40L (CD154) resulted in activation of the NF-
B and MAPK signaling pathways and up-regulation of cell surface markers and intracellular molecules associated with Ag processing and presentation. Concomitantly, the CD154-induced activation of CD40 in carcinoma cells was found to directly influence susceptibility to CTL-mediated killing. Thus, CD40 stimulation in cervical carcinoma cell lines expressing a TAP-dependent human papillomavirus 16 E6 Ag epitope resulted in their enhanced killing by specific CTLs. However, CD154 treatment of carcinoma cells expressing proteasome-dependent but TAP-independent Ags from the EBV-encoded BRLF1 and BMLF1 failed to increase tumor cell lysis by specific CTLs. Moreover, we demonstrate that chemotherapeutic agents that suppress protein synthesis and reverse the CD40-mediated dissociation of the translational repressor eukaryotic initiation factor 4E-binding protein from the initiation factor eukaryotic initiation factor 4E, such as 5-fluorouracil, etoposide, and quercetin, dramatically increase the susceptibility of cervical carcinoma cells to CD40L-induced apoptosis. Taken together, these observations demonstrate the functional expression of CD40 in epithelial tumors of the cervix and support the clinical exploitation of the CD40 pathway for the treatment of cervical cancer through its multiple effects on tumor cell growth, apoptosis, and immune recognition.
This article has been cited by other articles:
|
|
 |
|
  A. Moschonas, M. Kouraki, P. G. Knox, E. Thymiakou, D. Kardassis, and A. G. Eliopoulos CD40 Induces Antigen Transporter and Immunoproteasome Gene Expression in Carcinomas via the Coordinated Action of NF-{kappa}B and of NF-{kappa}B-Mediated De Novo Synthesis of IRF-1 Mol. Cell. Biol., October 15, 2008; 28(20): 6208 - 6222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bergmann and P. P. Pandolfi Giving blood: a new role for CD40 in tumorigenesis J. Exp. Med., October 30, 2006; 203(11): 2409 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Davies, T. W. Mak, L. S. Young, and A. G. Eliopoulos TRAF6 Is Required for TRAF2-Dependent CD40 Signal Transduction in Nonhemopoietic Cells Mol. Cell. Biol., November 15, 2005; 25(22): 9806 - 9819. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
