| Description |
Here, we developed a murine bone metastasis model with Renca cells obtained from soft fibrin gel-induced three-dimensional (3D) tumor spheres with a tumor-repopulating phenotype and found that a stable form of vitamin C, L-ascorbic acid 2-phosphate sesquimagnesium (APM), significantly inhibited the growth of renal cancer stem-like cells in vitro and the progression of RCC bone metastasis in vivo. Single-cell RNA sequencing revealed that APM induced cell cycle arrest and decreased the metastatic competence of cancer cells. Moreover, APM remodeled the tumor microenvironment, suppressed osteoclast differentiation and enhanced neutrophil-mediated cytotoxicity. This work elucidates a comprehensive and highresolution profile of the antitumor effects of vitamin C in the bone metastatic microenvironment and provides a rationale for clinical trials with vitamin C in patients with bone metastatic RCC. |