Skip Navigation



Carcinogenesis Advance Access published online on November 4, 2004
Carcinogenesis, doi:10.1093/carcin/bgh329
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
26/2/309    most recent
bgh329v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Zou, J.
Right arrow Articles by Deutscher, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zou, J.
Right arrow Articles by Deutscher, S. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received August 24, 2004
Revised October 7, 2004
Accepted October 26, 2004

CANCER BIOLOGY

Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion1

Jun Zou 1, Vladislav V. Glinsky 2, Linda A. Landon 3, Leslie Matthews 4, and Susan L. Deutscher 2*

1 Department of Biochemistry, University of Missouri, Columbia, Missouri 65212
2 Department of Biochemistry University of Missouri, Columbia, Missouri 65212; Harry S. Truman Memorial Veteran's Hospital, Columbia, MO 65201
3 Harry S. Truman Memorial Veteran's Hospital, Columbia, MO 65201
4 Dana-Farber Cancer Institute, Boston, MA 02115

* To whom correspondence should be addressed.
Susan L. Deutscher, E-mail: deutschers{at}missouri.edu


  Abstract

Intravascular cancer cell adhesion plays a significant role in the metastatic process. Studies indicate that galectin-3, a member of the galectin family of soluble animal lectins, is involved in carbohydrate-mediated metastatic cell heterotypic (between carcinoma cells and endothelium) and homotypic (between carcinoma cells) adhesion via interactions with the tumor-specific Thomsen-Friedenreich glycoantigen (TFAg). We hypothesized that blocking the galectin-3 carbohydrate recognition domain with synthetic peptides would significantly reduce metastasis-associated carcinoma cell adhesion. To test this hypothesis, we identified peptide antagonists of galectin-3 carbohydrate recognition domain using combinatorial bacteriophage display technology. The peptides bound with high affinity to purified, recombinant galectin-3 protein (Kd {cong}17~80 nM) and to cell surface galectin-3. Experiments with a series of recombinant serially truncated galectin-3 mutants indicated that the peptides bound the carbohydrate recognition domain of galectin-3. Furthermore, the peptides did not bind the carbohydrate recognition domain of other galectins and plant lectins. Synthetic galectin-3 carbohydrate recognition domain-specific peptides blocked the interaction between galectin-3 and TFAg, and significantly inhibited rolling and stable heterotypic adhesion of human MDA-MB-435 breast carcinoma cells to endothelial cells in flow, as well as homotypic tumor cell aggregation. These results demonstrate that carbohydrate-mediated metastasis-associated tumor cell adhesion could be inhibited efficiently with short synthetic peptides, which do not mimic naturally occurring glycoepitopes, yet bind to the galectin-3 carbohydrate recognition domain with high affinity and specificity.

Keywords: metastasis-related adhesion; phage display; carbohydrate-dependent adhesion; synthetic peptide inhibitors; carbohydrate recognition.

1 This work was supported in part by a Merit Review Award from the Veterans Administration, the Department of Defense DAMD17-03-1-0130 (SLD) and NIH P50 CA103130-01 (Wynn Volkert).


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JNMHome page
S. R. Kumar and S. L. Deutscher
111In-Labeled Galectin-3-Targeting Peptide as a SPECT Agent for Imaging Breast Tumors
J. Nucl. Med., May 1, 2008; 49(5): 796 - 803.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
V. L. Thijssen, S. Hulsmans, and A. W. Griffioen
The Galectin Profile of the Endothelium: Altered Expression and Localization in Activated and Tumor Endothelial Cells
Am. J. Pathol., February 1, 2008; 172(2): 545 - 553.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. L. J. L. Thijssen, F. Poirier, L. G. Baum, and A. W. Griffioen
Galectins in the tumor endothelium: opportunities for combined cancer therapy
Blood, October 15, 2007; 110(8): 2819 - 2827.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. L. J. L. Thijssen, R. Postel, R. J. M. G. E. Brandwijk, R. P. M. Dings, I. Nesmelova, S. Satijn, N. Verhofstad, Y. Nakabeppu, L. G. Baum, J. Bakkers, et al.
Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy
PNAS, October 24, 2006; 103(43): 15975 - 15980.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
G. A. Rabinovich, A. Cumashi, G. A. Bianco, D. Ciavardelli, I. Iurisci, M. D'Egidio, E. Piccolo, N. Tinari, N. Nifantiev, and S. Iacobelli
Synthetic lactulose amines: novel class of anticancer agents that induce tumor-cell apoptosis and inhibit galectin-mediated homotypic cell aggregation and endothelial cell morphogenesis
Glycobiology, March 1, 2006; 16(3): 210 - 220.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.