論文 - 詳細
| RRC ID | 43702 |
|---|---|
| 著者 | Fowler JA, Mundy GR, Lwin ST, Edwards CM. |
| タイトル | Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. |
| ジャーナル | Cancer Res |
| Abstract |
The rapid progression of multiple myeloma is dependent upon cellular interactions within the bone marrow microenvironment. In vitro studies suggest that bone marrow stromal cells (BMSC) can promote myeloma growth and survival and osteolytic bone disease. However, it is not possible to recreate all cellular aspects of the bone marrow microenvironment in an in vitro system, and the contributions of BMSCs to myeloma pathogenesis in an intact, immune competent, in vivo system are unknown. To investigate this, we used a murine myeloma model that replicates many features of the human disease. Coinoculation of myeloma cells and a BMSC line, isolated from myeloma-permissive mice, into otherwise nonpermissive mice resulted in myeloma development, associated with tumor growth within bone marrow and osteolytic bone disease. In contrast, inoculation of myeloma cells alone did not result in myeloma. BMSCs inoculated alone induced osteoblast suppression, associated with an increase in serum concentrations of the Wnt signaling inhibitor, Dkk1. Dkk1 was highly expressed in BMSCs and in myeloma-permissive bone marrow. Knockdown of Dkk1 expression in BMSCs decreased their ability to promote myeloma and the associated bone disease in mice. Collectively, our results show novel roles of BMSCs and BMSC-derived Dkk1 in the pathogenesis of multiple myeloma in vivo. |
| 巻・号 | 72(9) |
| ページ | 2183-9 |
| 公開日 | 2012-5-1 |
| DOI | 10.1158/0008-5472.CAN-11-2067 |
| PII | 0008-5472.CAN-11-2067 |
| PMID | 22374979 |
| PMC | PMC3775476 |
| MeSH | Animals Bone Marrow Cells / metabolism Bone Marrow Cells / pathology* Female Gene Knockdown Techniques Intercellular Signaling Peptides and Proteins / biosynthesis* Intercellular Signaling Peptides and Proteins / genetics Mice Mice, Inbred C57BL Multiple Myeloma / genetics Multiple Myeloma / metabolism Multiple Myeloma / pathology* Stromal Cells / metabolism Stromal Cells / pathology* Tumor Microenvironment Wnt Proteins / antagonists & inhibitors |
| IF | 9.727 |
| 引用数 | 51 |
| 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 | 13 |
| 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 | ST2(RCB0224) |