|
|
 Previous Article | Table of Contents | Next Article 
Mechanisms of Growth Control of Kaposi's Sarcoma-Associated Herpes
Virus-Associated Primary Effusion Lymphoma Cells
Hiroya Asou,
Jonathan W. Said,
Rong Yang,
Reinhold Munker,
Dorothy
J. Park,
Nanao Kamada, and
H. Phillip Koeffler
From the Division of Hematology/Oncology and Pathology, Cedars-Sinai
Medical Center, UCLA School of Medicine, Los Angeles, CA; and the
Department of Cancer Cytogenetics, Division of Molecular Biology,
Research Institute for Radiation Biology and Medicine, Hiroshima
University, Hiroshima, Japan.
Primary effusion lymphoma (PEL) is a distinct clinicopathologic
entity associated with Kaposi's sarcoma-associated herpes virus
(KSHV). Several cytokines, including interleukin-6 (IL-6), basic
fibroblast growth factor (bFGF), and platelet-derived growth factor
(PDGF) may be important for survival of KS cells. However, little is
known about the interaction of cytokines with KSHV-infected lymphocytes
from PEL. Therefore, we investigated what cytokines were produced by
KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine
receptors were expressed by these cells, what response these cells had
to selected cytokines, and what was the effect of IL-6 antisense
phosphorothioated oligonucleotides. Reverse transcriptase-polymerase
chain reaction (RT-PCR) and protein studies showed that these three
cell lines produced IL-10, IL-6, and the receptors for IL-6. The
granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1 ,
IL-8, IL-12, bFGF, PDGF, and c-kit transcripts were not
detected in the cell lines. High levels (0.7 to 5 ng/mL/106
cells/48 hours) of IL-6 protein were consistently detected in supernatants of the cell lines by enzyme-linked immunosorbent assay
(ELISA) tests. In clonogenic assays, interferon- (IFN-) and
IFN- suppressed the clonal growth of the PEL cells, but GM-CSF, IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for several autocrine loops that have been suggested to occur
in KS. Experiments using antisense oligonucleotides showed that the
clonal growth of KS-1 and BC-1 was nearly 100% inhibited by IL-6
antisense oligonucleotides (10 µmol/L), but not at all by either
oligonucleotides ( 10 µmol/L) to IL-6 sense, IL-6 scrambled, viral
IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL-6
antisense oligonucleotides had no effect on two B-cell lymphoma cell
lines, which were not infected with KSHV. Addition of IL-6 antibody did
not inhibit clonal growth of any of the cell lines. Taken together, we
have defined the cytokines and their receptors expressed on PEL cells
and have found that these cells synthesized IL-6 and IL-6 receptors;
interruption of this pathway by IL-6 antisense oligonucleotides
specifically prevented the growth of these cells. These findings will
offer potential new therapeutic strategies for PEL.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2475-2481
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y.-J. Zhang, R. S. Bonaparte, D. Patel, D. A. Stein, and P. L. Iversen
Blockade of viral interleukin-6 expression of Kaposi's sarcoma-associated herpesvirus
Mol. Cancer Ther.,
March 1, 2008;
7(3):
712 - 720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Sin, D. Roy, L. Wang, M. R. Staudt, F. D. Fakhari, D. D. Patel, D. Henry, W. J. Harrington Jr, B. A. Damania, and D. P. Dittmer
Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
Blood,
March 1, 2007;
109(5):
2165 - 2173.
[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]
|
|
|
|
|
|
|
S. T. Perry and T. Compton
Kaposi's Sarcoma-Associated Herpesvirus Virions Inhibit Interferon Responses Induced by Envelope Glycoprotein gpK8.1
J. Virol.,
November 15, 2006;
80(22):
11105 - 11114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Arguello, S. Paz, E. Hernandez, C. Corriveau-Bourque, L. M. Fawaz, J. Hiscott, and R. Lin
Leukotriene A4 Hydrolase Expression in PEL Cells Is Regulated at the Transcriptional Level and Leads to Increased Leukotriene B4 Production.
J. Immunol.,
June 1, 2006;
176(11):
7051 - 7061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Xie, H. Pan, S. Yoo, and S.-J. Gao
Kaposi's Sarcoma-Associated Herpesvirus Induction of AP-1 and Interleukin 6 during Primary Infection Mediated by Multiple Mitogen-Activated Protein Kinase Pathways
J. Virol.,
December 15, 2005;
79(24):
15027 - 15037.
[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]
|
|
|
|
|
|
|
C. McCormick and D. Ganem
The Kaposin B Protein of KSHV Activates the p38/MK2 Pathway and Stabilizes Cytokine mRNAs
Science,
February 4, 2005;
307(5710):
739 - 741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Glaunsinger and D. Ganem
Highly Selective Escape from KSHV-mediated Host mRNA Shutoff and Its Implications for Viral Pathogenesis
J. Exp. Med.,
August 2, 2004;
200(3):
391 - 398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. An, Y. Sun, and M. B. Rettig
Transcriptional coactivation of c-Jun by the KSHV-encoded LANA
Blood,
January 1, 2004;
103(1):
222 - 228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Duplomb, B. Chaigne-Delalande, P. Vusio, S. Raher, Y. Jacques, A. Godard, and F. Blanchard
Soluble Mannose 6-Phosphate/Insulin-Like Growth Factor II (IGF-II) Receptor Inhibits Interleukin-6-Type Cytokine-Dependent Proliferation by Neutralization of IGF-II
Endocrinology,
December 1, 2003;
144(12):
5381 - 5389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Klein, A. Gloghini, G. Gaidano, A. Chadburn, E. Cesarman, R. Dalla-Favera, and A. Carbone
Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts
Blood,
May 15, 2003;
101(10):
4115 - 4121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cannon, N. J. Philpott, and E. Cesarman
The Kaposi's Sarcoma-Associated Herpesvirus G Protein-Coupled Receptor Has Broad Signaling Effects in Primary Effusion Lymphoma Cells
J. Virol.,
December 6, 2002;
77(1):
57 - 67.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Deng, J. T. Chu, M. B. Rettig, O. Martinez-Maza, and R. Sun
Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression
Blood,
August 13, 2002;
100(5):
1919 - 1921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Li and J. Nicholas
Identification of Amino Acid Residues of gp130 Signal Transducer and gp80 {alpha} Receptor Subunit That Are Involved in Ligand Binding and Signaling by Human Herpesvirus 8-Encoded Interleukin-6
J. Virol.,
May 3, 2002;
76(11):
5627 - 5636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Gwack, S. Hwang, C. Lim, Y. S. Won, C. H. Lee, and J. Choe
Kaposi's Sarcoma-associated Herpesvirus Open Reading Frame 50 Stimulates the Transcriptional Activity of STAT3
J. Biol. Chem.,
February 15, 2002;
277(8):
6438 - 6442.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. An, A. K. Lichtenstein, G. Brent, and M. B. Rettig
The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element
Blood,
January 15, 2002;
99(2):
649 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Liu, Y. Okruzhnov, H. Li, and J. Nicholas
Human Herpesvirus 8 (HHV-8)-Encoded Cytokines Induce Expression of and Autocrine Signaling by Vascular Endothelial Growth Factor (VEGF) in HHV-8-Infected Primary-Effusion Lymphoma Cell Lines and Mediate VEGF-Independent Antiapoptotic Effects
J. Virol.,
November 15, 2001;
75(22):
10933 - 10940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Perez and S. Rudoy
Anti-CD20 Monoclonal Antibody Treatment of Human Herpesvirus 8-Associated, Body Cavity-Based Lymphoma with an Unusual Phenotype in a Human Immunodeficiency Virus-Negative Patient
Clin. Vaccine Immunol.,
September 1, 2001;
8(5):
993 - 996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Li, H. Wang, and J. Nicholas
Detection of Direct Binding of Human Herpesvirus 8-Encoded Interleukin-6 (vIL-6) to both gp130 and IL-6 Receptor (IL-6R) and Identification of Amino Acid Residues of vIL-6 Important for IL-6R-Dependent and -Independent Signaling
J. Virol.,
April 1, 2001;
75(7):
3325 - 3334.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J Nicholas
Evolutionary aspects of oncogenic herpesviruses
Mol. Pathol.,
October 1, 2000;
53(5):
222 - 237.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. Aoki, R. Yarchoan, J. Braun, A. Iwamoto, and G. Tosato
Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions
Blood,
August 15, 2000;
96(4):
1599 - 1601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Pica, A. Volpi, A. Serafino, M. Fraschetti, O. Franzese, and E. Garaci
Autocrine nerve growth factor is essential for cell survival and viral maturation in HHV-8-infected primary effusion lymphoma cells
Blood,
May 1, 2000;
95(9):
2905 - 2912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Jones, Y. Aoki, Y. Chang, P. S. Moore, R. Yarchoan, and G. Tosato
Involvement of Interleukin-10 (IL-10) and Viral IL-6 in the Spontaneous Growth of Kaposi's Sarcoma Herpesvirus-Associated Infected Primary Effusion Lymphoma Cells
Blood,
October 15, 1999;
94(8):
2871 - 2879.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Wan, H. Wang, and J. Nicholas
Human Herpesvirus 8 Interleukin-6 (vIL-6) Signals through gp130 but Has Structural and Receptor-Binding Properties Distinct from Those of Human IL-6
J. Virol.,
October 1, 1999;
73(10):
8268 - 8278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Aoki, E. S. Jaffe, Y. Chang, K. Jones, J. Teruya-Feldstein, P. S. Moore, and G. Tosato
Angiogenesis and Hematopoiesis Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Interleukin-6
Blood,
June 15, 1999;
93(12):
4034 - 4043.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
