論文 - 詳細
| RRC ID | 38188 |
|---|---|
| 著者 | Shin SY, Nam JS, Lim Y, Lee YH. |
| タイトル | TNFα-exposed bone marrow-derived mesenchymal stem cells promote locomotion of MDA-MB-231 breast cancer cells through transcriptional activation of CXCR3 ligand chemokines. |
| ジャーナル | J Biol Chem |
| Abstract |
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are often recruited to solid tumors, integrate into the tumor stroma, and contribute to tumor development. TNFα is a major inflammatory cytokine present in the tumor microenvironment and has a profound influence on the progression of tumor development. This study was aimed to investigate the role of BM-MSCs in tumor promotion in response to TNFα. Quantitative real-time PCR arrays show that diverse cytokines/chemokines were induced in TNFα-treated BM-MSCs; in particular, CXCR3 ligand chemokines, including CXCL9, CXCL10, and CXCL11, were potently induced. A serial and site-directed mutation analysis in the CXCL9, CXCL10, and CXCL11 promoters revealed that NF-κB binding elements were responsible for TNFα-induced promoter activation of CXCR3 ligand chemokines. TNFα stimulated NF-κB activity, and ectopic expression of NF-κB enhanced TNFα-induced promoter activities of the CXCR3 ligand chemokines. Gel shift and supershift assays showed that NF-κB was associated with CXCR3 ligand chemokine promoters in response to TNFα treatment. All three CXCR3 ligand chemokines enhanced the migration and invasive motility of MDA-MB-231 breast cancer cells expressing CXCR3. Treatment of MDA-MB-231 cells with CXCL10 activated small GTPase of Rho family proteins, such as RhoA and Cdc42. CXCL9-, CXCL10-, or CXCL11-induced invasive capability of MDA-MB-231 cells was completely abrogated in the presence of a neutralizing anti-CXCR3 antibody in the culture medium. Moreover, CXCL9, CXCL10, and CXCL11 stimulated the expression of MMP-9, but not MMP-2, in MDA-MB-231 cells. These results suggest that BM-MSCs promote the locomotion of breast cancer cells through CXCR3 ligand-mediated actin rearrangement by TNFα in the tumor microenvironment. |
| 巻・号 | 285(40) |
| ページ | 30731-40 |
| 公開日 | 2010-10-1 |
| DOI | 10.1074/jbc.M110.128124 |
| PII | S0021-9258(19)88964-0 |
| PMID | 20650898 |
| PMC | PMC2945567 |
| MeSH | Bone Marrow Cells / metabolism* Bone Marrow Cells / pathology Breast Neoplasms / genetics Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Line, Tumor Cell Movement* Chemokines, CXC / biosynthesis* Chemokines, CXC / genetics Coculture Techniques Female Gene Expression Regulation, Neoplastic* Humans Ligands Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / biosynthesis Matrix Metalloproteinase 9 / genetics Mesenchymal Stem Cells / metabolism* Mesenchymal Stem Cells / pathology NF-kappa B / genetics NF-kappa B / metabolism Neoplasm Invasiveness Receptors, CXCR3 / genetics Receptors, CXCR3 / metabolism* Response Elements / genetics Tumor Necrosis Factor-alpha / metabolism* Tumor Necrosis Factor-alpha / pharmacology |
| IF | 4.238 |
| 引用数 | 56 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | human BM-MSCs |