Suppression of KSHV-induced angiopoietin-2 inhibits angiogenesis, infiltration of inflammatory cells, and tumor growth. Issue 15 (2nd August 2016)

• Record Type: Journal Article
• Authors: Yu, Xiaolan; Sha, Jingfeng; Xiang, Shao; Qin, Sanhai; Conrad, Patricia; Ghosh, Santosh K.; Weinberg, Aaron; Ye, Fengchun
• Is Part Of: Cell cycle. Volume 15:Issue 15(2016)
• Page Start: 2053
• Page End: 2065
• Publication Date: 2016-08-02
• Subjects: angiopoietin-2 -- angiogenesis -- inflammation -- and Kaposi's sarcoma -- KSHV; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1196303
• Languages: English
• ISSNs: 1538-4101

Abstract

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.