title: Cellular origin of Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus-induced cell reprogramming.
abstract: Kaposi's sarcoma (KS) is the most common malignancy in untreated HIV patients. KS is characterised by abnormal neoangiogenesis, inflammation, and proliferation of tumour cells [KS spindle cells (SCs)]. Kaposi's sarcoma-associated herpesvirus (KSHV) is the aetiological agent of KS. KS SCs are the predominant KSHV-infected cells in KS lesions. In this review, we report advances in understanding of the cellular origin of the KS SC, a contentious topic in KSHV research. KS SCs are now known to be of endothelial cell (EC) origin, phenotypically most similar to lymphatic ECs (LECs), but poorly differentiated. We focus on recent insights into KSHV's ability to exploit the normal differentiation pathway and intrinsic plasticity of ECs, through manipulation of EC-specific transcriptional regulators [i.e., prospero homeobox 1 (PROX1) and MAF] and discuss how this may contribute to viral persistence and KS sarcomagenesis.
authors.affiliation: UCL Cancer Institute, 72 Huntley Street, University College London, London WC1E 6BT, UK.
authors.forename: Laila
authors.initials: L
authors.lastname: Cancian
authors.forename: Amy
authors.initials: A
authors.lastname: Hansen
authors.forename: Chris
authors.initials: C
authors.lastname: Boshoff
mesh_terms: D002454:Cell Differentiation; D042783:Endothelial Cells / Q000473:pathology* / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000821:virology; D009858:Oncogenic Viruses / Q000235:genetics / Q000472:pathogenicity*; D012514:Sarcoma, Kaposi / Q000150:complications / Q000473:pathology* / Q000821:virology
keywords: KSHV/HHV8; Kaposi's sarcoma; cell differentiation; cell plasticity; endothelial cells; oncogenic viruses