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Upregulation of angiopoietin-like 4 by viral G protein-coupled receptor promotes angiogenesis and vascular permeability in Kaposi’s sarcoma
Infectious Agents and Cancervolume 5, Article number: A84 (2010)
Kaposi’s sarcoma (KS) is an enigmatic vascular tumor thought to be a consequence of dysregulated expression of the human herpesvirus-8 (HHV-8 or KSHV)-encoded G protein-coupled receptor (vGPCR) . Both human and vGPCR experimental KS lesions are characterized by prominent angiogenesis and vascular permeability attributed to the paracrine release of angiogenic mediators, most notably vascular endothelial growth factor (VEGF). To date, the relative contribution of these paracrine mediators to the angiogenic and exudative phenotype of KS lesions remains unclear. Here we show that vGPCR upregulated angiopoietin-like 4 (ANGPTL4) (Figure 1A, 1B, 1C) plays a prominent role in promoting the angiogenesis and increasing vascular permeability in this tumor. Inhibition of ANGPTL4 effectively blocks vGPCR promotion of angiogenesis and vascular permeability in vitro and tumorigenesis in vivo (Figure 1D , 1E, 1F, 1G , 1H).
These observations suggest that ANGPTL4 is a previously unrecognized target for the treatment of patients with KS. As angiogenesis and increased vessel permeability are common themes in all solid tumors, these results may have a broad impact on our understanding and treatment of cancer.
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This work was supported by grant R01CA119911 (National Cancer Institute, NIH). We thank Histoserv, Inc., for its assistance in the processing of the murine tissues. BCJ is a recipient of a predoctoral fellowship from the CNPq-Brazil.
This article has been published as part of Infectious Agents and Cancer Volume 5 Supplement 1, 2010: Proceedings of the 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI).The full contents of the supplement are available online at http://www.biomedcentral.com/1750-9378/5?issue=S1.