Suppression of KSHV-induced angiopoietin-2 inhibits angiogenesis,infiltration of inflammatory cells,and tumor growth |
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| Authors: | Xiaolan Yu Jingfeng Sha Shao Xiang Sanhai Qin Patricia Conrad Santosh K Ghosh |
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| Institution: | 1. Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, USA;2. Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, College of Life Sciences, Hubei University, Wuhan, Hubei, China;3. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, OH, USA |
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| Abstract: | Kaposi's sarcoma (KS) is a highly angiogenic and inflammatory neoplasia. The angiogenic and inflammatory cytokine angiopoietin-2 (Ang-2) is strongly expressed in KS due to Kaposi's sarcoma-associated herpesvirus (KSHV) infection. In the present study, we determined how Ang-2 contributes to development of KS by using telomerase-immortalized human umbilical vein endothelial cells (TIVE) as a model, which become malignantly transformed and express increased levels of Ang-2 following KSHV infection. Ang-2 released from TIVE-KSHV cells induces tyrosine phosphorylation of Tie-2 receptor from both human and mouse endothelial cells and promotes angiogenesis in nude mice. Functional inhibition or expressional “knock-down” of Ang-2 in these cells blocks angiogenesis and inhibits tumor growth. Ang-2 suppression also reduces the numbers of infiltrating monocytes/macrophages in tumors. In transwell-based cell migration assays, Ang-2 indeed enhances migration of human monocytes in a dose-dependent manner. These results underscore a pivotal role of KSHV-induced Ang-2 in KS tumor development by promoting both angiogenesis and inflammation. Our data also suggest that selective drug targeting of Ang-2 may be used for treatment of KS. |
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| Keywords: | angiopoietin-2 angiogenesis inflammation and Kaposi's sarcoma KSHV |
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