兰克尔
骨转移
癌症研究
转移
医学
乳腺癌
癌症
癌细胞
内科学
肿瘤科
免疫学
骨吸收
破骨细胞
骨保护素
骨溶解
骨癌
作者
Bora Kim,Yong Jin Cho,Mineon Park,Wonbong Lim
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2021-09-21
被引量:1
标识
DOI:10.1097/cji.0000000000000393
摘要
Breast cancer cells often metastasize to bone. Accumulating evidence suggests that inhibiting the receptor activator of nuclear factor-κB ligand (RANKL) not only leads to reduced bone metastasis of breast cancer but also has antitumoral effects. Here, we used mutant receptor activator of nuclear factor-κB ligand (RANKLM) as a vaccine for active immunization to induce antibodies for immunotherapy of bone metastatic cancer. We investigated whether anti-RANKL antibodies inhibit osteolytic bone metastasis in vitro and in a murine model. MC3T3 cells stimulated by MDA-MB-231 culture medium secreted growth differentiation factor-15 (GDF-15), which induced the nuclear factor-κB signaling cascade. In addition, RANKLM treatment-induced reduction of intraosseous growth of MDA-MB-231 cells correlated with decreased GDF-15 expression, a reduced number of osteolytic lesions, and slower tumor progression. In addition, vaccination with RANKLM led to significant improvement in overall survival and skeletal metastasis in tumor-bearing mice. Induction of anti-RANKL antibodies by RANKLM decreased GDF-15 production by deactivating nuclear factor-κB signaling, which in turn inhibited metastasis of MDA-MB-231 cells to bone. Taken together, the results demonstrate a role for RANKLM immunization in preventing bone metastasis of breast cancer.
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