Manipulation of endothelial cells by KSHV: implications for angiogenesis and aberrant vascular differentiation.
Kaposi sarcoma (KS), a viral cancer associated to Kaposi sarcoma herpesvirus (KSHV) infection, is currently the most common tumor in men in sub-Saharan Africa. KS is an angiogenic tumor and characterized by the presence of aberrant vascular structures in the lesion. Although our understanding of how KSHV causes the aberrant differentiation of endothelial cells and the typical vascular abnormalities in KS tumors is far from complete, the experimental evidence reviewed here provides a comprehensive description of the role of KSHV in the pathogenesis of this unusual tumor. In contrast to other tumor viruses, whose interference with cellular processes relating to cell cycle, apoptosis and DNA damage may be at the heart of their oncogenic properties, KSHV may cause KS primarily by its ability to engage with the differentiation and function of endothelial cells. Although the intracellular pathways engaged by KSHV in the endothelial cells are being explored as drug targets, a better understanding of the impact of KSHV on endothelial cell differentiation and vasculogenesis is needed before the encouraging findings can form the basis for new targeted therapeutic approaches to KS.
Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 University of Helsinki, Finland; Foundation for the Finnish Cancer Institute, Helsinki, Finland; Section of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK. Electronic address: paivi.ojala@helsinki.fi.
Päivi M
PM
Ojala
Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Thomas F
TF
Schulz
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010641:Phenotype; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology
Angiogenesis; Cellular differentiation; Endothelial cells; KSHV; Kaposi's sarcoma; Lymphatic vasculature; Signaling; Tumor virus