Immunization With RANKL Inhibits Osteolytic Bone Metastasis in Breast Cancer. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Kim, Bora; Cho, Yong Jin; Park, Mineon; Lim, Wonbong
• Is Part Of: Journal of immunotherapy. Volume 45:Issue 1(2022)
• Publication Date: 2022-01
• Subjects: receptor activator for NF-κB ligand (RANKL) -- breast cancer -- bone metastasis -- growth differentiation factor-15 (GDF-15); Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000393
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : 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 (RANKL M ) 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, RANKL M 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 RANKL M led to significant improvement in overall survival and skeletal metastasis in tumor-bearing mice. Induction of anti-RANKL antibodies by RANKL M 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 RANKL M immunization in preventing bone metastasis of breast cancer. Abstract : Supplemental Digital Content is available in the text.