Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma.
The biology of Kaposi sarcoma is poorly understood because the dominant cell type in Kaposi sarcoma lesions is not known. We show by gene expression microarrays that neoplastic cells of Kaposi sarcoma are closely related to lymphatic endothelial cells (LECs) and that Kaposi sarcoma herpesvirus (KSHV) infects both LECs and blood vascular endothelial cells (BECs) in vitro. The gene expression microarray profiles of infected LECs and BECs show that KSHV induces transcriptional reprogramming of both cell types. The lymphangiogenic molecules VEGF-D and angiopoietin-2 were elevated in the plasma of individuals with acquired immune deficiency syndrome and Kaposi sarcoma. These data show that the gene expression profile of Kaposi sarcoma resembles that of LECs, that KSHV induces a transcriptional drift in both LECs and BECs and that lymphangiogenic molecules are involved in the pathogenesis of Kaposi sarcoma.
Wang
Hsei-Wei
HW
Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical Research, Cruciform Building, Gower Street, University College London, London WC1E 6BT, UK.
Trotter
Matthew W B
MW
Lagos
Dimitrios
D
Bourboulia
Dimitra
D
Henderson
Stephen
S
Mäkinen
Taija
T
Elliman
Stephen
S
Flanagan
Adrienne M
AM
Alitalo
Kari
K
Boshoff
Chris
C
D002460:Cell Line; D004727:Endothelium / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D020869:Gene Expression Profiling; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction