Effects of myeloid specific deficiency of FBXW7 on lung metastasis of murine melanoma

Abstract

Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed. B16F10 tumor colonies in the lungs were counted. The myeloid cells were analyzed by flow cytometry. Results: Myeloid-specific deficiency of FBXW7 mice were generated successfully, as FBXW7 expressions in peritoneal macrophages and bone marrow-derived macrophages (BMDMs) of Lysm+FBXW7f/f mice were knockdown. Flow cytometry results showed the deletion of FBXW7 in myeloid lineages did not affect the development of myeloid immune cell subsets. Metastasis was reduced in Lysm+FBXW7 f/f mice compared with control mice. The number of tumor colonies was 165±42, 122±12 respectively. The proportion of metastasis-associated macrophages (MAM) in the lungs of Lysm+FBXW7 f/f mice was reduced [(23.15±7.59)% vs (13.13±2.26)%], while the proportion of resident macrophages was increased [(5.426±0.42)% vs (10.42±1.90)%]. The proportion of myeloid-derived suppressor cells in the lung showed no difference between Lysm-FBXW7f/f and Lysm+FBXW7 f/f mice. Conclusion: Myeloid-specific deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and the mechanism may be associated with regulation of MAM in the metastatic tumor lesions.