論文 - 詳細
| RRC ID | 68719 |
|---|---|
| 著者 | Kinoshita H, Hirata Y, Nakagawa H, Sakamoto K, Hayakawa Y, Takahashi R, Nakata W, Sakitani K, Serizawa T, Hikiba Y, Akanuma M, Shibata W, Maeda S, Koike K. |
| タイトル | Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis. |
| ジャーナル | PLoS One |
| Abstract |
Interleukin-6 (IL-6) is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/-)) mice with wild-type (WT) mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/-) mice, compared with WT mice. Impaired tumor development in IL-6(-/-) mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1) receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis. |
| 巻・号 | 8(4) |
| ページ | e60914 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0060914 |
| PII | PONE-D-12-15460 |
| PMID | 23593346 |
| PMC | PMC3625204 |
| MeSH | Animals Cell Communication* / drug effects Cell Differentiation / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Transformation, Neoplastic / drug effects Cell Transformation, Neoplastic / metabolism Cell Transformation, Neoplastic / pathology* Culture Media, Conditioned / pharmacology Disease Models, Animal Epithelial Cells / drug effects Epithelial Cells / metabolism* Epithelial Cells / pathology* Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Humans Interleukin-6 / deficiency Interleukin-6 / metabolism* Methylnitrosourea Mice Models, Biological Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology STAT3 Transcription Factor / metabolism Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology* Stromal Cells / drug effects Stromal Cells / metabolism Stromal Cells / pathology |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | MKN45(RCB1001) MKN74(RCB1002) |