Table of Contents Author Guidelines Submit a Manuscript
Sarcoma
Volume 2011, Article ID 847409, 15 pages
http://dx.doi.org/10.1155/2011/847409
Research Article

Potential for Modulation of the Fas Apoptotic Pathway by Epidermal Growth Factor in Sarcomas

1Department of Orthopaedics, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, USA
2Sarcoma Services, Center for Children, Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, USA
3Divison of Pediatric Oncology, The University of Utah, Salt Lake City, UT 84112, USA

Received 24 June 2011; Revised 22 August 2011; Accepted 23 August 2011

Academic Editor: Luca Sangiorgi

Copyright © 2011 David E. Joyner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

One important mechanism by which cancer cells parasitize their host is by escaping apoptosis. Thus, selectively facilitating apoptosis is a therapeutic mechanism by which oncotherapy may prove highly advantageous. One major apoptotic pathway is mediated by Fas ligand (FasL). The death-inducing signaling Ccmplex (DISC) and subsequent death-domain aggregations are created when FasL is bound by its receptor thereby enabling programmed cell death. Conceptually, if a better understanding of the Fas pathway can be garnered, an oncoselective prodeath therapeutic approach can be tailored. Herein, we propose that EGF and CTGF play essential roles in the regulation of the Fas apoptotic pathway in sarcomas. Tumor and in vitro data suggest viable cells counter the prodeath signal induced by FasL by activating EGF, which in turn induces prosurvival CTGF. The prosurvival attributes of CTGF ultimately predominate over the death-inducing FasL. Cells destined for elimination inhibit this prosurvival response via a presently undefined pathway. This scenario represents a novel role for EGF and CTGF as regulators of the Fas pathway in sarcomas.