دورية أكاديمية
Conversion of Osteoclasts into Bone-Protective, Tumor-Suppressing Cells
| العنوان: | Conversion of Osteoclasts into Bone-Protective, Tumor-Suppressing Cells |
|---|---|
| المؤلفون: | Li, Ke-Xin, Sun, Xun, Li, Bai-Yan, Yokota, Hiroki |
| المساهمون: | Biomedical Engineering, School of Engineering and Technology |
| المصدر: | PMC |
| بيانات النشر: | MDPI |
| سنة النشر: | 2021 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | CD44, Hsp90ab1, TGFβ, Wnt signaling, Bone metastasis, Breast cancer, Enolase 1, iTS cells, Osteoclasts, Polyubiquitin C |
| الوصف: | Osteoclasts are a driver of a vicious bone-destructive cycle with breast cancer cells. Here, we examined whether this vicious cycle can be altered into a beneficial one by activating Wnt signaling with its activating agent, BML284. The conditioned medium, derived from Wnt-activated RAW264.7 pre-osteoclast cells (BM CM), reduced the proliferation, migration, and invasion of EO771 mammary tumor cells. The same inhibitory effect was obtained with BML284-treated primary human macrophages. In a mouse model, BM CM reduced the progression of mammary tumors and tumor-induced osteolysis and suppressed the tumor invasion to the lung. It also inhibited the differentiation of RANKL-stimulated osteoclasts and enhanced osteoblast differentiation. BM CM was enriched with atypical tumor-suppressing proteins such as Hsp90ab1 and enolase 1 (Eno1). Immunoprecipitation revealed that extracellular Hsp90ab1 interacted with latent TGFβ (LAP-TGFβ) as an inhibitor of TGFβ activation, while Hsp90ab1 and Eno1 interacted and suppressed tumor progression via CD44, a cell-adhesion receptor and a cancer stem cell marker. This study demonstrated that osteoclast-derived CM can be converted into a bone-protective, tumor-suppressing agent by activating Wnt signaling. The results shed a novel insight on the unexplored function of osteoclasts as a potential bone protector that may develop an unconventional strategy to combat bone metastasis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Cancers; Li KX, Sun X, Li BY, Yokota H. Conversion of Osteoclasts into Bone-Protective, Tumor-Suppressing Cells. Cancers (Basel). 2021;13(22):5593. Published 2021 Nov 9. doi:10.3390/cancers13225593; https://hdl.handle.net/1805/32081Test |
| الإتاحة: | https://doi.org/10.3390/cancers13225593Test https://hdl.handle.net/1805/32081Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.58671ECF |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |