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PMID: 11555581 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma.

Masood R, Cai J, Tulpule A, Zheng T, Hamilton A, Sharma S, Espina BM, Smith DL, Gill PS

Abstract

Kaposi's sarcoma (KS) is the most common tumor associated with HIV-1 infection. Here, we report the expression, regulation, and biological effect of interleukin (IL)-8 in KS. AIDS-KS cell lines expressed higher levels of IL-8 than either human umbilical vein endothelial cells (HUVECs), human aortic smooth muscle (AoSM) cells or fibroblast cells (T1). The inflammatory cytokine IL-1beta up-regulated IL-8 expression in a time- and concentration-dependent manner in KS cell lines. IL-8 antisense oligonucleotides specifically reduced IL-8 mRNA and protein levels and inhibited KS cell growth in a dose-dependent manner. In addition, supernatant from a KS cell line induced the growth of HUVECs and angiogenesis in chicken chorioallantoic membrane assays, both of which were inhibited by IL-8 neutralizing antibody. Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology Biomarkers, Tumor/analysis Cell Division/drug effects Cell Line Culture Media, Conditioned/pharmacology DNA, Antisense/pharmacology Dose-Response Relationship, Drug Gene Expression Regulation, Neoplastic/drug effects Growth Substances/genetics,metabolism Humans Immunohistochemistry Interleukin-1/pharmacology Interleukin-8/genetics,immunology,pharmacology Male Mice Mice, Inbred BALB C Mice, Nude Neovascularization, Physiologic/drug effects Oligonucleotides/pharmacology RNA, Messenger/drug effects,genetics,metabolism RNA, Neoplasm/drug effects,genetics,metabolism Receptors, Interleukin-8A/analysis,genetics Recombinant Proteins/pharmacology Reverse Transcriptase Polymerase Chain Reaction Sarcoma, Kaposi/genetics,metabolism,prevention & control Tumor Cells, Cultured Up-Regulation/drug effects Xenograft Model Antitumor Assays
Chemicals
Antibodies, Monoclonal Biomarkers, Tumor Culture Media, Conditioned DNA, Antisense Growth Substances Interleukin-1 Interleukin-8 Oligonucleotides RNA, Messenger RNA, Neoplasm Receptors, Interleukin-8A Recombinant Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Masood R
University of Southern California Keck School of Medicine, Los Angeles, California 90089-9172, USA. masood@hsc.usc.edu
Cai J
Tulpule A
Zheng T
Hamilton A
Sharma S
Espina B M
Smith D L
Gill P S
Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1078-0432
Published
2001-09-00
Pages
2693-702
Language
English
Region
United States
NLM ID
9502500
Subset
IM
Grants
NCI NIH HHS · CA79281 · United States
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