論文 - 詳細
| RRC ID | 37630 |
|---|---|
| 著者 | Ara T, Song L, Shimada H, Keshelava N, Russell HV, Metelitsa LS, Groshen SG, Seeger RC, DeClerck YA. |
| タイトル | Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. |
| ジャーナル | Cancer Res |
| Abstract |
Neuroblastoma, the second most common solid tumor in children, frequently metastasizes to the bone marrow and the bone. Neuroblastoma cells present in the bone marrow stimulate the expression of interleukin-6 (IL-6) by bone marrow stromal cells (BMSC) to activate osteoclasts. Here we have examined whether stromal-derived IL-6 also has a paracrine effect on neuroblastoma cells. An analysis of the expression of IL-6 and its receptor, IL-6R, in 11 neuroblastoma cell lines indicated the expression of IL-6 in 4 cell lines and of IL-6R in 9 cell lines. Treatment of IL-6R-positive cells with recombinant human IL-6 resulted in signal transducer and activator of transcription-3 and extracellular signal-regulated kinase-1/2 activation. Culturing IL-6R-positive neuroblastoma cells in the presence of BMSC or recombinant human IL-6 increased proliferation and protected tumor cells from etoposide-induced apoptosis, whereas it had no effect on IL-6R-negative tumor cells. In vivo, neuroblastoma tumors grew faster in the presence of a paracrine source of IL-6. IL-6 induced the expression of cyclooxygenase-2 in neuroblastoma cells with concomitant release of prostaglandin-E2, which increased the expression of IL-6 by BMSC. Supporting a role for stromal-derived IL-6 in patients with neuroblastoma bone metastasis, we observed elevated levels of IL-6 in the serum and bone marrow of 16 patients with neuroblastoma bone metastasis and in BMSC derived from these patients. Altogether, the data indicate that stromal-derived IL-6 contributes to the formation of a bone marrow microenvironment favorable to the progression of metastatic neuroblastoma. |
| 巻・号 | 69(1) |
| ページ | 329-37 |
| 公開日 | 2009-1-1 |
| DOI | 10.1158/0008-5472.CAN-08-0613 |
| PII | 69/1/329 |
| PMID | 19118018 |
| PMC | PMC2761219 |
| MeSH | Animals Apoptosis / drug effects Apoptosis / physiology Bone Marrow Cells / metabolism Bone Marrow Cells / pathology* Bone Marrow Neoplasms / mortality Bone Marrow Neoplasms / pathology Bone Marrow Neoplasms / secondary Bone Neoplasms / metabolism Bone Neoplasms / pathology Bone Neoplasms / secondary Cell Growth Processes / drug effects Cell Growth Processes / physiology Cell Line, Tumor Humans Interleukin-6 / biosynthesis* Interleukin-6 / pharmacology Mice Mice, Inbred NOD Mice, SCID Neuroblastoma / metabolism Neuroblastoma / pathology* Receptors, Interleukin-6 / biosynthesis Recombinant Proteins / pharmacology STAT3 Transcription Factor / metabolism Stromal Cells / metabolism Stromal Cells / pathology |
| IF | 9.727 |
| 引用数 | 107 |
| WOS 分野 | ONCOLOGY |
| 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 | 9 |
| 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 | NB19(RCB0479) |