التفاصيل البيبلوغرافية
| العنوان: |
Conversion of Osteoclasts into Bone-Protective, Tumor-Suppressing Cells |
| المؤلفون: |
Ke-Xin Li, Xun Sun, Bai-Yan Li, Hiroki Yokota |
| المصدر: |
Cancers; Volume 13; Issue 22; Pages: 5593 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
osteoclasts, breast cancer, bone metastasis, iTS cells, Wnt signaling, Hsp90ab1, enolase 1, polyubiquitin C, TGFβ, CD44 |
| 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: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
https://dx.doi.org/10.3390/cancers13225593Test |
| DOI: |
10.3390/cancers13225593 |
| الإتاحة: |
https://doi.org/10.3390/cancers13225593Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.FC86A2F8 |
| قاعدة البيانات: |
BASE |
