| 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
|
| リソース情報 |
| ヒト・動物細胞 |
NB19(RCB0479) |
