The Kaposi's sarcoma progenitor enigma: KSHV-induced MEndT–EndMT axis. Issue 3 (March 2023)

• Record Type: Journal Article
• Authors: Naipauer, Julian; Mesri, Enrique A.
• Is Part Of: Trends in molecular medicine. Volume 29:Issue 3(2023)
• Page Start: 188
• Page End: 200
• Publication Date: 2023-03
• Subjects: Kaposi´s sarcoma herpesvirus -- virus oncogenesis -- endothelial-to-mesenchymal differentiation axis -- angiogenesis -- sarcomagenesis; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2022.12.003
• Languages: English
• ISSNs: 1471-4914

Abstract

Highlights: Endothelial-to-mesenchymal (EndMT) and mesenchymal-to-endothelial (MEndT) transitions have been described in tumors as a source of mesenchymal stroma and tumor vasculogenesis/angiogenesis, respectively. Kaposi's sarcoma herpes virus (KSHV) can reprogram endothelial or mesenchymal cells one into the other after infection through endothelial-to-mesenchymal or mesenchymal-to-endothelial transitions. KS remains potentially life-threatening for patients with advanced or antiretroviral-therapy-resistant KS. The identification of the KS progenitor primary cell type and the environmental conditions leading to sarcomagenesis is still under debate. These would allow the development of more accurate and physiologically relevant KS animal models to test new-targeted therapies for KS. KSHV induces the mesenchymal–endothelial differentiation axis in KS progenitor cells, indicating the importance of this mechanism in viral oncogenesis. Abstract: Endothelial-to-mesenchymal transition has been described in tumors as a source of mesenchymal stroma, while the reverse process has been proposed in tumor vasculogenesis and angiogenesis. A human oncogenic virus, Kaposi's sarcoma herpes virus (KSHV), can regulate both processes in order to transit through this transition 'boulevard' when infecting KS oncogenic progenitor cells. Endothelial or mesenchymal circulating progenitor cells can serve as KS oncogenic progenitors recruited by inflammatory cytokines because KSHV can reprogram one into the other through endothelial-to-mesenchymal and mesenchymal-to-endothelial transitions. Through these novel insights, the identity of the potential oncogenic progenitor of KS is revealed while gaining knowledge of the biology of the mesenchymal-endothelial differentiation axis and pointing to this axis as a therapeutic target in KS.