RRC ID 43342
Author Fukaya Y, Shimada H, Wang LC, Zandi E, DeClerck YA.
Title Identification of galectin-3-binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma.
Journal J Biol Chem
Abstract 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.
Volume 283(27)
Pages 18573-81
Published 2008-7-4
DOI 10.1074/jbc.M803115200
PII M803115200
PMID 18450743
MeSH Antigens, Neoplasm Biomarkers, Tumor Bone Marrow Cells / metabolism* Bone Marrow Cells / pathology Carrier Proteins / biosynthesis* Carrier Proteins / genetics Carrier Proteins / pharmacology Cell Line, Tumor Culture Media, Conditioned / pharmacology Down-Regulation / drug effects Galectin 3 / genetics Galectin 3 / metabolism Galectin 3 / pharmacology Gene Expression Regulation, Neoplastic / drug effects Glycoproteins / biosynthesis* Glycoproteins / genetics Glycoproteins / pharmacology Humans Interleukin-6 / biosynthesis* Interleukin-6 / genetics Interleukin-6 / pharmacology MAP Kinase Signaling System* / drug effects MAP Kinase Signaling System* / genetics Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Neoplasm Proteins / pharmacology Neuroblastoma / genetics Neuroblastoma / metabolism* Recombinant Proteins / biosynthesis Recombinant Proteins / genetics Recombinant Proteins / pharmacology Stromal Cells / metabolism Stromal Cells / pathology
IF 4.238
Times Cited 47
Human and Animal Cells