HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 36, 26408-26418, September 8, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/36/26408    most recent M602853200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seidler, D. G. Articles by Iozzo, R. V. Search for Related Content PubMed PubMed Citation Articles by Seidler, D. G. Articles by Iozzo, R. V. Social Bookmarking                      What's this?

Decorin Protein Core Inhibits in Vivo Cancer Growth and Metabolism by Hindering Epidermal Growth Factor Receptor Function and Triggering Apoptosis via Caspase-3 Activation^*

Daniela G. Seidler, Silvia Goldoni, Christopher Agnew, Christopher Cardi, Mathew L. Thakur, Rick T. Owens^¶, David J. McQuillan^¶, and Renato V. Iozzo^||1

From the Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, the Radiopharmaceutical Research Center, Department of Radiation, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, the ^¶LifeCell Corporation, Branchburg, New Jersey 08876, and the ^||Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Decorin is not only a regulator of matrix assembly but also a key signaling molecule that modulates the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR). Decorin evokes protracted internalization of the EGFR via a caveolar-mediated endocytosis, which leads to EGFR degradation and attenuation of its signaling pathway. In this study, we tested if systemic delivery of decorin protein core would affect the biology of an orthotopic squamous carcinoma xenograft. After tumor engraftment, the animals were given intraperitoneal injections of either vehicle or decorin protein core (2.5-10 mg kg^-1) every 2 days for 18-38 days. This regimen caused a significant and dose-dependent inhibition of the tumor xenograft growth, with a concurrent decrease in mitotic index and a significant increase in apoptosis. Positron emission tomography showed that the metabolic activity of the tumor xenografts was significantly reduced by decorin treatment. Decorin protein core specifically targeted the tumor cells enriched in EGFR and caused a significant down-regulation of EGFR and attenuation of its activity. In vitro studies showed that the uptake of decorin by the A431 cells was rapid and caused a protracted down-regulation of the EGFR to levels similar to those observed in the tumor xenografts. Furthermore, decorin induced apoptosis via activation of caspase-3. This could represent an additional mechanism whereby decorin might influence cell growth and survival.

Received for publication, March 27, 2006 , and in revised form, July 5, 2006.

^* This work was supported in part by National Institutes of Health Grants RO1 CA39481 and RO1 CA47282 and Department of the Army Grants DAMD17-00-1-0425 (to R. V. I.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Materials and Methods and Figs. S1 and S2.

¹ To whom correspondence should be addressed: Dept. of Pathology, Anatomy and Cell Biology, Rm. 249 JAH, Thomas Jefferson University, Philadelphia, PA 19107. Tel.: 215-503-2208; Fax: 215-923-7969; E-mail: iozzo{at}mail.jci.tju.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Li, A. Pennisi, and S. Yaccoby Role of decorin in the antimyeloma effects of osteoblasts Blood, July 1, 2008; 112(1): 159 - 168. [Abstract] [Full Text] [PDF]

				A. Zafiropoulos, D. Nikitovic, P. Katonis, A. Tsatsakis, N. K. Karamanos, and G. N. Tzanakakis Decorin-Induced Growth Inhibition Is Overcome through Protracted Expression and Activation of Epidermal Growth Factor Receptors in Osteosarcoma Cells Mol. Cancer Res., May 1, 2008; 6(5): 785 - 794. [Abstract] [Full Text] [PDF]

				Z. Ferdous, V. M. Wei, R. Iozzo, M. Hook, and K. J. Grande-Allen Decorin-transforming Growth Factor- Interaction Regulates Matrix Organization and Mechanical Characteristics of Three-dimensional Collagen Matrices J. Biol. Chem., December 7, 2007; 282(49): 35887 - 35898. [Abstract] [Full Text] [PDF]

				B. Gellersen, J. Briese, M. Oberndorfer, K. Redlin, A. Samalecos, D.-U. Richter, T. Loning, H.-M. Schulte, and A.-M. Bamberger Expression of the Metastasis Suppressor KAI1 in Decidual Cells at the Human Maternal-Fetal Interface: Regulation and Functional Implications Am. J. Pathol., January 1, 2007; 170(1): 126 - 139. [Abstract] [Full Text] [PDF]