دورية أكاديمية

IGF-1R mediates crosstalk between nasopharyngeal carcinoma cells and osteoclasts and promotes tumor bone metastasis

التفاصيل البيبلوغرافية
العنوان: IGF-1R mediates crosstalk between nasopharyngeal carcinoma cells and osteoclasts and promotes tumor bone metastasis
المؤلفون: Kaifan Yang, Yanjun Hu, Yuanyuan Feng, Kaiqun Li, Ziyan Zhu, Shuyi Liu, Yanling Lin, Bin Yu
المصدر: Journal of Experimental & Clinical Cancer Research, Vol 43, Iss 1, Pp 1-17 (2024)
بيانات النشر: BMC, 2024.
سنة النشر: 2024
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: Nasopharyngeal carcinoma, Bone metastasis, IGF-1R, Osteoclasts, GM-CSF, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Abstract Background Nasopharyngeal carcinoma (NPC) poses a significant health burden in specific regions of Asia, and some of NPC patients have bone metastases at the time of initial diagnosis. Bone metastasis can cause pathologic fractures and pain, reducing patients' quality of life, and is associated with worse survival. This study aims to unravel the complex role of insulin-like growth factor 1 receptor (IGF-1R) in NPC bone metastasis, offering insights into potential therapeutic targets. Methods We assessed IGF-1R expression in NPC cells and explored its correlation with bone metastasis. Experiments investigated the impact of osteoclast-secreted IGF-1 on the IGF-1R/AKT/S6 pathway in promoting NPC cell proliferation within the bone marrow. Additionally, the reciprocal influence of tumor-secreted Granulocyte–macrophage colony-stimulating factor (GM-CSF) on osteoclast differentiation and bone resorption was examined. The effects of IGF-1 neutralizing antibody, IGF-1R specific inhibitor (NVP-AEW541) and mTORC inhibitor (rapamycin) on nasopharyngeal carcinoma bone metastasis were also explored in animal experiments. Results Elevated IGF-1R expression in NPC cells correlated with an increased tendency for bone metastasis. IGF-1, secreted by osteoclasts, activated the IGF-1R/AKT/S6 pathway, promoting NPC cell proliferation in the bone marrow. Tumor-secreted GM-CSF further stimulated osteoclast differentiation, exacerbating bone resorption. The IGF-1 neutralizing antibody, NVP-AEW541 and rapamycin were respectively effective in slowing down the rate of bone metastasis and reducing bone destruction. Conclusion The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1756-9966
Relation: https://doaj.org/toc/1756-9966
DOI: 10.1186/s13046-024-02970-8
URL الوصول: https://doaj.org/article/81a708c571a94299bd412251f6f0c31c
رقم الأكسشن: edsdoj.81a708c571a94299bd412251f6f0c31c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:17569966
DOI:10.1186/s13046-024-02970-8