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PMID: 11326314 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice.

Neoplasia (New York, N.Y.) ·Vol. 3 ·No. 1 ·2001-00-00 ·Pages 33-42

Kim SJ, Uehara H, Karashima T, Mccarty M, Shih N, Fidler IJ

Abstract

We determined whether the expression of interleukin-8 (IL-8) by human prostate cancer cells correlates with induction of angiogenesis, tumorigenicity, and production of metastasis. Low and high IL-8-producing clones were isolated from the heterogeneous PC-3 human prostate cancer cell line. The secretion of IL-8 protein correlated with transcriptional activity and levels of IL-8 mRNA. All PC-3 cells expressed both IL-8 receptors, CXCR1 and CXCR2. The low and high IL-8-producing clones were injected into the prostate of nude mice. Titration studies indicated that PC-3 cells expressing high levels of IL-8 were highly tumorigenic, producing rapidly growing, highly vascularized prostate tumors with and a 100% incidence of lymph node metastasis. Low IL-8-expressing PC-3 cells were less tumorigenic, producing slower growing and less vascularized primary tumors and a significantly lower incidence of metastasis. In situ hybridization (ISH) analysis of the tumors for expression of genes that regulate angiogenesis and metastasis showed that the expression level of IL-8, matrix metalloproteinases, vascular endothelial growth factor (VEGF), and E-cadherin corresponded with microvascular density and biological behavior of the prostate cancers in nude mice. Collectively, the data show that the expression level of IL-8 in human prostate cancer cells is associated with angiogenesis, tumorigenicity, and metastasis.

MeSH Terms
Animals Blotting, Northern Cadherins/metabolism DNA Primers/chemistry Endothelial Growth Factors/metabolism Fibroblast Growth Factor 2/metabolism Humans In Situ Hybridization Interleukin-8/metabolism Lymphatic Metastasis Lymphokines/metabolism Male Matrix Metalloproteinase 2/metabolism Mice Mice, Inbred BALB C Mice, Nude Neoplasm Invasiveness Neoplasm Transplantation Neovascularization, Pathologic/metabolism,pathology Prostatic Neoplasms/blood supply,metabolism,pathology RNA, Messenger/genetics,metabolism Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Cadherins DNA Primers Endothelial Growth Factors Interleukin-8 Lymphokines RNA, Messenger Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Fibroblast Growth Factor 2 Matrix Metalloproteinase 2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kim S J
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Uehara H
Karashima T
Mccarty M
Shih N
Fidler I J
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1038/sj.neo.7900124
Published
2001-00-00
Pages
33-42
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1505029
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA16672 · United States
NCI NIH HHS · R35-CA42107 · United States
External Links
PubMed source DOI: 10.1038/sj.neo.7900124 PMC Full Text
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