期刊
CELL HOST & MICROBE
卷 10, 期 6, 页码 577-590出版社
CELL PRESS
DOI: 10.1016/j.chom.2011.10.011
关键词
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资金
- Academy of Finland
- University of Helsinki Foundations
- Finnish Cancer Foundations
- Sigrid Juselius Foundation
- European Union [LSHC-CT-2005-018704]
- Finnish Cultural Foundation and Paulo Foundation
- Helsinki Biomedical Graduate School
- Finnish Graduate School of Musculoskeletal Disorders and Biomaterials
- Cancer Foundation Finland sr [110105] Funding Source: researchfish
- Cancer Research UK [13100] Funding Source: researchfish
Kaposi sarcoma (KS), an angioproliferative disease associated with Kaposi sarcoma herpesvirus (KSHV) infection, harbors a diversity of cell types ranging from endothelial to mesenchymal cells of unclear origin. We developed a three-dimensional cell model for KSHV infection and used it to demonstrate that KSHV induces transcriptional reprogramming of lymphatic endothelial cells to mesenchymal cells via endothelial-to-mesenchymal transition (EndMT). KSHV-induced EndMT was initiated by the viral proteins vFLIP and vGPCR through Notch pathway activation, leading to gain of membrane-type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive properties and concomitant changes in viral gene expression. Mesenchymal markers and MT1-MMP were found codistributed with a KSHV marker in the same cells from primary KS biopsies. Our data explain the heterogeneity of cell types within KS lesions and suggest that KSHV-induced EndMT may contribute to KS development by giving rise to infected, invasive cells while providing the virus a permissive cellular microenvironment for efficient spread.
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