This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Masood, R. Articles by Flore, O. Search for Related Content PubMed PubMed Citation Articles by Masood, R. Articles by Flore, O.

(American Journal of Pathology. 2002;160:23-29.)
© 2002 American Society for Investigative Pathology

Short Communications

Human Herpesvirus-8-Transformed Endothelial Cells Have Functionally Activated Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor

Rizwan Masood^*, Ethel Cesarman, D. Lynne Smith, Parkash S. Gill^* and Ornella Flore

From the Departments of Medicine
and Pathology,^*
Keck School of Medicine, University of Southern California, Los Angeles, California; the Department of Microbiology,
New York University School of Medicine, New York, New York; and the Department of Pathology,
Cornell University Weill Medical College, New York, New York

Kaposi’s sarcoma is a vascular tumor commonly associated with human immunodeficiency virus (HIV)-1 and human herpesvirus (HHV-8) also known as Kaposi’s sarcoma-associated herpesvirus. The principal features of this tumor are abnormal proliferation of vascular structures lined with spindle-shaped endothelial cells. HHV-8 may transform a subpopulation of endothelial cells in vitro via viral and cellular gene expression. We hypothesized that among the cellular genes, vascular endothelial growth factors (VEGFs) and their cognate receptors may be involved in viral-mediated transformation. We have shown that HHV-8-transformed endothelial cells (EC-HHV-8) express higher levels of VEGF, VEGF-C, VEGF-D, and PlGF in addition to VEGF receptors-1, -2, and -3. Furthermore, antibodies to VEGF receptor-2 inhibited cell proliferation and viability. Similarly, inhibition of VEGF gene expression with antisense oligonucleotides inhibited EC-HHV-8 cell proliferation/viability. The growth and viability of primary endothelial cells and a fibroblast cell line however were unaffected by either the VEGF receptor-2 antibody or the VEGF antisense oligodeoxynucleotides. VEGF and VEGF receptors are thus induced in EC-HHV-8 and participate in the transformation. Inhibitors of VEGF may thus modulate the disease process during development and progression.

This article has been cited by other articles:

				L. Wang and B. Damania Kaposi's Sarcoma-Associated Herpesvirus Confers a Survival Advantage to Endothelial Cells Cancer Res., June 15, 2008; 68(12): 4640 - 4648. [Abstract] [Full Text] [PDF]

				I Petrache, K Diab, K S Knox, H L Twigg III, R S Stephens, S Flores, and R M Tuder HIV associated pulmonary emphysema: a review of the literature and inquiry into its mechanism Thorax, May 1, 2008; 63(5): 463 - 469. [Abstract] [Full Text] [PDF]

				F.-C. Ye, D. J. Blackbourn, M. Mengel, J.-P. Xie, L.-W. Qian, W. Greene, I-T. Yeh, D. Graham, and S.-J. Gao Kaposi's Sarcoma-Associated Herpesvirus Promotes Angiogenesis by Inducing Angiopoietin-2 Expression via AP-1 and Ets1 J. Virol., April 15, 2007; 81(8): 3980 - 3991. [Abstract] [Full Text] [PDF]

				M. M. Brinkmann, M. Pietrek, O. Dittrich-Breiholz, M. Kracht, and T. F. Schulz Modulation of Host Gene Expression by the K15 Protein of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., January 1, 2007; 81(1): 42 - 58. [Abstract] [Full Text] [PDF]

				Y. Murakami, S. Yamagoe, K. Noguchi, Y. Takebe, N. Takahashi, Y. Uehara, and H. Fukazawa Ets-1-dependent Expression of Vascular Endothelial Growth Factor Receptors Is Activated by Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus through Interaction with Daxx J. Biol. Chem., September 22, 2006; 281(38): 28113 - 28121. [Abstract] [Full Text] [PDF]

				X. Zhang, J. F. Wang, B. Chandran, K. Persaud, B. Pytowski, J. Fingeroth, and J. E. Groopman Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection J. Biol. Chem., July 15, 2005; 280(28): 26216 - 26224. [Abstract] [Full Text] [PDF]

				S. M. Akula, P. W. Ford, A. G. Whitman, K. E. Hamden, B. A. Bryan, P. P. Cook, and J. A. McCubrey B-Raf-dependent expression of vascular endothelial growth factor-A in Kaposi sarcoma-associated herpesvirus-infected human B cells Blood, June 1, 2005; 105(11): 4516 - 4522. [Abstract] [Full Text] [PDF]

				H. Zhang, V. Vakil, M. Braunstein, E. L. P. Smith, J. Maroney, L. Chen, K. Dai, J. R. Berenson, M. M. Hussain, U. Klueppelberg, et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance Blood, April 15, 2005; 105(8): 3286 - 3294. [Abstract] [Full Text] [PDF]

				K. E. Hamden, P. W. Ford, A. G. Whitman, O. F. Dyson, S.-Y. Cheng, J. A. McCubrey, and S. M. Akula Raf-Induced Vascular Endothelial Growth Factor Augments Kaposi's Sarcoma-Associated Herpesvirus Infection J. Virol., December 1, 2004; 78(23): 13381 - 13390. [Abstract] [Full Text] [PDF]

				Y. Aoki and G. Tosato HIV-1 Tat enhances Kaposi sarcoma-associated herpesvirus (KSHV) infectivity Blood, August 1, 2004; 104(3): 810 - 814. [Abstract] [Full Text] [PDF]

				L. Wang, N. Wakisaka, C. C Tomlinson, S. M DeWire, S. Krall, J. S Pagano, and B. Damania The Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) K1 Protein Induces Expression of Angiogenic and Invasion Factors Cancer Res., April 15, 2004; 64(8): 2774 - 2781. [Abstract] [Full Text] [PDF]

				A. SODHI, S. MONTANER, and J. S. GUTKIND Does dysregulated expression of a deregulated viral GPCR trigger Kaposi's sarcomagenesis? FASEB J, March 1, 2004; 18(3): 422 - 427. [Abstract] [Full Text] [PDF]

				M. Zangari, E. Anaissie, A. Stopeck, A. Morimoto, N. Tan, J. Lancet, M. Cooper, A. Hannah, G. Garcia-Manero, S. Faderl, et al. Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma Clin. Cancer Res., January 1, 2004; 10(1): 88 - 95. [Abstract] [Full Text] [PDF]

				C. D. Cool, P. R. Rai, M. E. Yeager, D. Hernandez-Saavedra, A. E. Serls, T. M. Bull, M. W. Geraci, K. K. Brown, J. M. Routes, R. M. Tuder, et al. Expression of Human Herpesvirus 8 in Primary Pulmonary Hypertension N. Engl. J. Med., September 18, 2003; 349(12): 1113 - 1122. [Abstract] [Full Text] [PDF]

				L. A. Dourmishev, A. L. Dourmishev, D. Palmeri, R. A. Schwartz, and D. M. Lukac Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis Microbiol. Mol. Biol. Rev., June 1, 2003; 67(2): 175 - 212. [Abstract] [Full Text] [PDF]

				H.-G. Guo, M. Sadowska, W. Reid, E. Tschachler, G. Hayward, and M. Reitz Kaposi's Sarcoma-Like Tumors in a Human Herpesvirus 8 ORF74 Transgenic Mouse J. Virol., February 15, 2003; 77(4): 2631 - 2639. [Abstract] [Full Text] [PDF]