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Kaposi sarcoma herpesvirus–induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma

Nature Genetics volume 36, pages 687–693 (2004)Cite this article

Abstract

The biology of Kaposi sarcoma is poorly understood because the dominant cell type in Kaposi sarcoma lesions is not known1,2,3,4. 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)5,6 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.

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Figure 1: GEM data for Kaposi sarcoma and cell groups.
Figure 2: Relationships between the Kaposi sarcoma expression signature and cell groups.
Figure 3: Tropism of KSHV.
Figure 4: Reprogramming of LECs and BECs by KSHV.
Figure 5: ELISA of ANG2, VEGF and VEGF-D levels.

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Acknowledgements

We thank the AIDS-Malignancy Bank of the US National Cancer Institute for providing the Kaposi sarcoma biopsy samples used in this study; M. Byers, S. Crane, D. MacDonald, D.B. Guiliano, A. Godfrey and R. Dunbar for technical expertise; J. Vieira for providing the BCBL-1 cell line producing KSHV-GFP; and R. Ambinder for providing the JSC-1 cell line. We apologize to the many scientists whose work we did not cite due to space constraints. This work is supported by Wellcome Trust, European Union, Cancer Research UK and the Medical Research Council.

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Authors and Affiliations

  1. Cancer Research UK, Viral Oncology Group, Wolfson Institute for Biomedical Research, Cruciform Building, Gower Street, University College London, London, WC1E 6BT, UK

    Hsei-Wei Wang, Matthew W B Trotter, Dimitrios Lagos, Dimitra Bourboulia, Stephen Henderson, Stephen Elliman & Chris Boshoff

  2. Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Finland

    Taija Mäkinen & Kari Alitalo

  3. Institute of Orthopaedics, University College London, UK

    Adrienne M Flanagan

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  1. Hsei-Wei Wang
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Correspondence to Chris Boshoff.

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Supplementary information

Supplementary Fig. 1

Hierarchical cluster of 35 samples and a filtered set of 5894 genes. (PDF 1860 kb)

Supplementary Fig. 2

Infection of KSHV in LECs and BECs. (PDF 158 kb)

Supplementary Table 1

Gene differentially expressed between KS and normal skin, or between LECs and BECs. (XLS 665 kb)

Supplementary Table 2

Average linkage distances between each sample group. (PDF 6 kb)

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Wang, HW., Trotter, M., Lagos, D. et al. Kaposi sarcoma herpesvirus–induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma. Nat Genet 36, 687–693 (2004). https://doi.org/10.1038/ng1384

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