WISP-3 Stimulates VEGF-C-Dependent Lymphangiogenesis in Human Chondrosarcoma Cells by Inhibiting miR-196a-3p Synthesis.

Chih-Yang Lin,Chih-Hsin Tang,Shih-Wei Wang,Jeng-Hung Guo,Shih-Chia Liu,Chen-Yu Yang,Wen-Chun Sun,Yi-Chin Fong,Cheng-Ta Lai,Huai-Ching Tai

doi:10.3390/biomedicines9101330

Abstract

Chondrosarcoma is a malignant bone tumor with high metastatic potential. Lymphangiogenesis is a critical biological step in cancer metastasis. WNT1-inducible signaling pathway protein 3 (WISP-3) regulates angiogenesis and facilitates chondrosarcoma metastasis, but the role of WISP-3 in chondrosarcoma lymphangiogenesis is unclear. In this study, incubation of chondrosarcoma cells with WISP-3 increased the production of VEGF-C, an important lymphangiogenic factor. Conditioned medium from WISP-3-treated chondrosarcoma cells significantly enhanced lymphatic endothelial cell tube formation. WISP-3-induced stimulation of VEGF-C-dependent lymphangiogenesis inhibited miR-196a-3p synthesis in the ERK, JNK, and p38 signaling pathways. This evidence suggests that the WISP-3/VEGF-C axis is worth targeting in the treatment of lymphangiogenesis in human chondrosarcoma.

Highlights

Our study has identified that WNT1-inducible signaling pathway protein 3 (WISP-3) increased VEGF-C production and facilitated lymphatic endothelial cells (LECs)
We initially found that WISP-3 treatment increased VEGF-C mRNA and secreted protein initially found that
WISP-3 and LECofmarkers and LYVE-1 (Figure 6E–I). These results indicate that and LYVE-1. These results indicate that inhibiting inhibiting WISP-3 lowers LEC lymphangiogenesis in vivo

Summary

Introduction

Chondrosarcomas are cartilage-forming tumors found typically in the femur, tibia, or pelvis [1,2], and these tumors metastasize to distant organs [1]. High-grade chondrosarcomas are prone to metastasize to the lungs [3,4] and lack effective therapeutic options [5], so it is imperative that research efforts search for potentially effective treatments. Tumor metastasis involves the movement of cancer cells from the primary site and their establishment in other organs [6,7]. A growing body of research has highlighted

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Conclusion