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

• Published in: Journal of experimental & clinical cancer research Vol. 43; no. 1; p. 46
• Main Authors: Yang, Kaifan, Hu, Yanjun, Feng, Yuanyuan, Li, Kaiqun, Zhu, Ziyan, Liu, Shuyi, Lin, Yanling, Yu, Bin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.02.2024; BioMed Central; BMC
• Subjects: Animal experimentation; Animals; Antibodies; Antibodies, Neutralizing; Bone marrow; Bone metastasis; Bone Neoplasms; Bone Resorption; Breast cancer; Cancer; Carcinoma; Cell cycle; Cell growth; Cell Line, Tumor; Experiments; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use; Health aspects; Humans; IGF-1R; Insulin; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor I - therapeutic use; Insulin-like growth factors; Kinases; Macrophage colony stimulating factor; Medical prognosis; Metastasis; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - pathology; Nasopharyngeal Neoplasms - pathology; Osteoclasts; Osteoclasts - metabolism; Physiology; Prostate; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Quality of Life; Sirolimus - pharmacology; Throat cancer; Viral antibodies; China; Nasopharyngeal carcinoma; Osteoclasts; Bone metastasis; IGF-1R; GM-CSF
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-024-02970-8

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. 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. 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. 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.