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

J. Biol. Chem., Vol. 283, Issue 27, 18573-18581, July 4, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/27/18573    most recent M803115200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fukaya, Y. Articles by DeClerck, Y. A. Search for Related Content PubMed PubMed Citation Articles by Fukaya, Y. Articles by DeClerck, Y. A. Social Bookmarking                      What's this?

Identification of Galectin-3-binding Protein as a Factor Secreted by Tumor Cells That Stimulates Interleukin-6 Expression in the Bone Marrow Stroma^*

Yasushi Fukaya, Hiroyuki Shimada, Ling-Chi Wang^¶, Ebrahim Zandi^¶, and Yves A. DeClerck^||1

From the Division of Hematology-Oncology and Department of Pediatrics, Department of Pathology, ^¶Department of Molecular Microbiology and Immunology, and ^||Department of Biochemistry and Molecular Biology, Keck School of Medicine of the University of Southern California and The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California 90027

We have previously demonstrated that neuroblastoma cells increase the expression of interleukin-6 by bone marrow stromal cells and that stimulation does not require cell-cell contact. In this study we report the purification and identification of a protein secreted by neuroblastoma cells that stimulates interleukin-6 production by stromal cells. Using a series of chromatographic purification steps including heparin-affinity, ion exchange, and molecular sieve chromatography followed by trypsin digestion and liquid chromatography tandem mass spectrometry, we identified in serum-free conditioned medium of neuroblastoma cells several secreted peptides including galectin-3-binding protein, also known as 90-kDa Mac-2-binding protein. We demonstrated the presence of the galectin-3-binding protein in the conditioned medium of several neuroblastoma cell lines and in chromatographic fractions with interleukin-6 stimulatory activity. Consistently, bone marrow stromal cells express galectin-3, the receptor for galectin-3-binding protein. Supporting a role for galectin-3-binding protein in stimulating interleukin-6 expression in bone marrow stromal cells, we observed that recombinant galectin-3-binding protein stimulated interleukin-6 expression in these cells and that interleukin-6 stimulation by neuroblastoma-conditioned medium was inhibited in the presence of lactose or a neutralizing anti-galectin-3 antibody. Down-regulation of galectin-3-binding protein expression in neuroblastoma cells also decreased the interleukin-6 stimulatory activity of the conditioned medium on bone marrow stromal cells. We also provide evidence that stimulation of interleukin-6 by galectin-3-binding protein involves activation of the Erk1/2 pathway. The data, thus, identifies galectin-3-binding protein as a factor secreted by neuroblastoma cells that stimulates the expression of interleukin-6 in bone marrow stromal cells and provides a novel function for this protein in cancer progression.

Received for publication, April 23, 2008

^* 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.

¹ To whom correspondence should be addressed: Childrens Hospital Los Angeles, 4650 Sunset Blvd., MailStop 54, Los Angeles, CA 90027. Tel.: 323-361-2150; Fax: 323-361-4902; E-mail: declerck{at}usc.edu.

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