1. Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.
- Author
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Song CY, Hsieh SL, Yang SY, Lin CY, Wang SW, Tsai CH, Lo YS, Fong YC, and Tang CH
- Subjects
- Humans, Animals, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Mice, Cytokines metabolism, Male, Female, MAP Kinase Signaling System, Chondrosarcoma metabolism, Chondrosarcoma genetics, Chondrosarcoma pathology, Lymphangiogenesis genetics, MicroRNAs genetics, MicroRNAs metabolism, Nicotinamide Phosphoribosyltransferase metabolism, Nicotinamide Phosphoribosyltransferase genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Vascular Endothelial Growth Factor D metabolism, Vascular Endothelial Growth Factor D genetics, Bone Neoplasms metabolism, Bone Neoplasms pathology, Bone Neoplasms genetics
- Abstract
Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.
- Published
- 2024
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