論文 - 詳細
| RRC ID | 43342 |
|---|---|
| 著者 | Fukaya Y, Shimada H, Wang LC, Zandi E, DeClerck YA. |
| タイトル | Identification of galectin-3-binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma. |
| ジャーナル | 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. |
| 巻・号 | 283(27) |
| ページ | 18573-81 |
| 公開日 | 2008-7-4 |
| DOI | 10.1074/jbc.M803115200 |
| PII | S0021-9258(20)81457-4 |
| 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 |
| 引用数 | 47 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 10 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | NB19(RCB0479) |