Thrombospondin 1 Triggers Osteosarcoma Cell Metastasis and Tumor Angiogenesis |
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Authors: | Yue Kui Jian Huan Ye Zhu Xing Lin Wu Bo Li |
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Institution: | Affiliated People’s Hospital of Guizhou Medical University, Guiyang, P.R. China |
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Abstract: | Osteosarcomas, especially those with metastatic or unresectable disease, have limited treatment options. The
antitumor effects of pharmacologic inhibitors of angiogenesis in osteosarcomas are hampered in patients by
the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis.
Here we demonstrated that thrombospondin 1 (TSP-1) is a potent inhibitor of the growth and metastasis of
the osteosarcoma cell line MG-63. Moreover, we demonstrate that upregulation of TSP-1 facilitated expression of vasculostatin in MG-63 cells. In angiogenesis assays, overexpression of TSP-1 inhibited MG-63 cells
and induced tube formation of human umbilical vein endothelial cells (HUVECs) in a CD36-dependent fashion. Finally, in xenografted tumors, we observed that TSP-1 overexpression inhibited angiogenesis and tumor
growth. These results provided strong evidence for an important role of the TSP-1/CD36/vasculostatin signaling axis in mediating the antiangiogenic activity of osteosarcoma. |
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Keywords: | TSP-1 Osteosarcoma Metastasis Angiogenesis CD36 |
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