Amphiregulin Promotes Vascular Endothelial Growth Factor-C Expression and Lymphangiogenesis through STAT3 Activation in Human Chondrosarcoma Cells

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Yu-Wen HuangChih-Hsin Tang

Abstract

Chondrosarcoma is the second most common primary malignancy of bone, characterized by a high metastatic potential. Increasing clinical data highlight the important role played by lymphangiogenesis in cancer metastasis. Amphiregulin (AR) has been implicated in tumor metastasis and lymphangiogenesis, but its association with vascular endothelial growth factor-C (VEGF-C) expression and lymphangiogenesis in chondrosarcoma is unclear. We used qPCR, ELISA and Western blotting to detect AR-induced VEGF-C expression in chondrosarcoma cells. Lymphangiogenesis was investigated by lymphatic endothelial cells (LECs) migration and tube formation. An in vivo experiment examined AR expression in tumor-associated lymphangiogenesis. In this study, we found that both AR and VEGF-C expression correlated with tumor stage and were significantly higher than levels found in normal cartilage. Exogenous AR promoted VEGF-C expression in chondrosarcoma cells in a time- and dose-dependent manner and subsequently increased migration and tube formation of LECs. AR also increased VEGF-C expression and lymphangiogenesis through the Src/MEK/ERK/STAT3 signaling pathway. However, it is unclear as to how an EGFR ligand (AR) induces activation of the Src kinase. K...Continue Reading

Citations

Aug 30, 2019·Expert Review of Anticancer Therapy·Iona J MacDonaldChih-Hsin Tang
Aug 31, 2019·Pathology, Research and Practice·Jiajia JiangZhenqing Feng
Feb 15, 2021·Cardiovascular Diabetology·Seshagiri Rao NandulaSabyasachi Sen

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