Kaposi's Sarcoma-Associated Herpesvirus Downregulates Transforming Growth Factor β2 To Promote Enhanced Stability of Capillary-Like Tube Formation

Abstract

Kaposi's sarcoma is a highly vascularized, endothelial cell-based tumor supporting large amounts of angiogenesis. There is evidence that KSHV, the etiologic agent of KS, induces aberrant angiogenesis. For example, KSHV induces stabilization of capillary-like tube formation in cultured endothelial cells. A clearer understanding of how KSHV regulates angiogenesis could provide potential therapeutic targets for KS. We found that KSHV downregulates TGF-β2, a cytokine related to TGF-β1 that is known to inhibit angiogenesis. The downregulation of this inhibitor promotes the stability of capillary-like tube formation insofar as adding back TGF-β2 to infected cells blocks KSHV-induced long-term tubule stability. Therefore, KSHV downregulation of TGF-β2 may increase aberrant vascularization in KS tumors through increased capillary formation and thereby aid in KS tumor promotion.