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PMID: 8675690 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice.

The Journal of clinical investigation ·Vol. 97 ·No. 12 ·1996-06-15 ·Pages 2792-802

Arenberg DA, Kunkel SL, Polverini PJ, Glass M, Burdick MD, Strieter RM

Abstract

The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.

MeSH Terms
Amino Acid Sequence Animals Carcinoma, Non-Small-Cell Lung/prevention & control Female Humans Interleukin-8/antagonists & inhibitors,physiology Lung Neoplasms/prevention & control Mice Mice, SCID Molecular Sequence Data Neoplasm Transplantation Neovascularization, Pathologic/prevention & control Transplantation, Heterologous Tumor Cells, Cultured
Chemicals
Interleukin-8
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Arenberg D A
Department of Internal Medicine (Division of Pulmonary and Critical Medicine), University of Michigan Medical School, Ann Arbor 48109, USA.
Kunkel S L
Polverini P J
Glass M
Burdick M D
Strieter R M
References (49)
49 references, click to expand
  1. Tumor dormancy in vivo by prevention of neovascularization.
    J Exp Med. 1972 Aug 1;136(2):261-76 PMID: 5043412
  2. Relation of vascular proliferation to tumor growth.
    Int Rev Exp Pathol. 1976;16:207-48 PMID: 783062
  3. Activated macrophages induce vascular proliferation.
    Nature. 1977 Oct 27;269(5631):804-6 PMID: 927505
  4. Stimulation of neovascularization by human rheumatoid synovial tissue macrophages.
    Arthritis Rheum. 1986 Apr;29(4):471-9 PMID: 2423091
  5. Angiogenic factors.
    Science. 1987 Jan 23;235(4787):442-7 PMID: 2432664
  6. Monokine-induced gene expression of a human endothelial cell-derived neutrophil chemotactic factor.
    Biochem Biophys Res Commun. 1988 Nov 15;156(3):1340-5 PMID: 3263857
  7. Induction of angiogenesis during the transition from hyperplasia to neoplasia.
    Nature. 1989 May 4;339(6219):58-61 PMID: 2469964
  8. Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts.
    J Biol Chem. 1989 Jun 25;264(18):10621-6 PMID: 2659589
  9. Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists.
    Biochem Biophys Res Commun. 1989 Nov 30;165(1):349-54 PMID: 2686646
  10. Cytokine-induced gene expression of a neutrophil chemotactic factor/IL-8 in human hepatocytes.
    J Immunol. 1990 Apr 1;144(7):2609-13 PMID: 2156928
  11. Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells.
    Am J Pathol. 1990 Apr;136(4):745-50 PMID: 2183623
  12. Interleukin-8 gene expression by a pulmonary epithelial cell line. A model for cytokine networks in the lung.
    J Clin Invest. 1990 Dec;86(6):1945-53 PMID: 2254454
  13. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.
    N Engl J Med. 1991 Jan 3;324(1):1-8 PMID: 1701519
  14. Cellular localization of interleukin-8 and its inducer, tumor necrosis factor-alpha in psoriasis.
    Am J Pathol. 1991 Jan;138(1):129-40 PMID: 1702929
  15. Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils.
    J Biol Chem. 1991 Jun 5;266(16):10666-71 PMID: 2037605
  16. Properties of the novel proinflammatory supergene "intercrine" cytokine family.
    Annu Rev Immunol. 1991;9:617-48 PMID: 1910690
  17. Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8.
    Kidney Int. 1991 Jul;40(1):86-90 PMID: 1921160
  18. Interleukin-8 as a macrophage-derived mediator of angiogenesis.
    Science. 1992 Dec 11;258(5089):1798-801 PMID: 1281554
  19. Interleukin-8. A corneal factor that induces neovascularization.
    Am J Pathol. 1992 Dec;141(6):1279-84 PMID: 1281615
  20. Identification of a novel granulocyte chemotactic protein (GCP-2) from human tumor cells. In vitro and in vivo comparison with natural forms of GRO, IP-10, and IL-8.
    J Immunol. 1993 Feb 1;150(3):1000-10 PMID: 8423327
  21. HuMig: a new human member of the chemokine family of cytokines.
    Biochem Biophys Res Commun. 1993 Apr 15;192(1):223-30 PMID: 8476424
  22. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.
    Nature. 1993 Apr 29;362(6423):841-4 PMID: 7683111
  23. Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo.
    Am J Respir Cell Mol Biol. 1993 May;8(5):562-72 PMID: 8481237
  24. Interleukin-8 stimulates angiogenesis in rats.
    Inflammation. 1993 Apr;17(2):135-43 PMID: 7684027
  25. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.
    Am J Pathol. 1993 Aug;143(2):401-9 PMID: 7688183
  26. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor.
    J Immunol. 1993 Sep 1;151(5):2667-75 PMID: 8360485
  27. The production of interleukin-1 receptor antagonist by human bronchogenic carcinoma.
    Am J Pathol. 1993 Sep;143(3):794-803 PMID: 8362978
  28. Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.
    J Exp Med. 1994 May 1;179(5):1409-15 PMID: 7513008
  29. Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice.
    Cancer Res. 1994 Jun 15;54(12):3242-7 PMID: 8205546
  30. Production of interleukin-10 by human bronchogenic carcinoma.
    Am J Pathol. 1994 Jul;145(1):18-25 PMID: 8030748
  31. Long-term impaired neutrophil migration in mice overexpressing human interleukin-8.
    J Clin Invest. 1994 Sep;94(3):1310-9 PMID: 7521886
  32. Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen.
    J Clin Invest. 1994 Sep;94(3):985-91 PMID: 8083383
  33. Cytokine networks in solid human tumors: regulation of angiogenesis.
    J Leukoc Biol. 1994 Oct;56(4):423-35 PMID: 7523556
  34. IL-8 specifically binds to endothelial but not to smooth muscle cells.
    J Immunol. 1995 Mar 1;154(5):2375-83 PMID: 7868904
  35. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo.
    J Exp Med. 1995 Jul 1;182(1):155-62 PMID: 7540647
  36. The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation.
    J Exp Med. 1995 Jul 1;182(1):219-31 PMID: 7790818
  37. Intratumor microvessel density as a prognostic factor in cancer.
    Am J Pathol. 1995 Jul;147(1):9-19 PMID: 7541613
  38. Distributions of melanoma growth stimulatory activity of growth-regulated gene and the interleukin-8 receptor B in human wound repair.
    Am J Pathol. 1995 Nov;147(5):1248-60 PMID: 7485389
  39. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis.
    J Biol Chem. 1995 Nov 10;270(45):27348-57 PMID: 7592998
  40. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides.
    Science. 1990 Jan 5;247(4938):77-9 PMID: 1688470
  41. Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking.
    Am J Respir Cell Mol Biol. 1991 Nov;5(5):493-501 PMID: 1931078
  42. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8.
    J Exp Med. 1991 Dec 1;174(6):1355-62 PMID: 1744577
  43. Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas.
    Am J Pathol. 1992 Feb;140(2):365-73 PMID: 1739130
  44. Thiol-containing compounds inhibit the production of monocyte/macrophage-derived angiogenic activity.
    Agents Actions. 1991 Nov;34(3-4):350-7 PMID: 1725690
  45. Relation of neovascularisation to metastasis of non-small-cell lung cancer.
    Lancet. 1992 Jul 18;340(8812):145-6 PMID: 1378165
  46. Interleukin-8 is produced in neoplastic and infectious diseases of the human central nervous system.
    Cancer Res. 1992 Aug 15;52(16):4297-305 PMID: 1643627
  47. Characterization of two high affinity human interleukin-8 receptors.
    J Biol Chem. 1992 Aug 15;267(23):16283-7 PMID: 1379593
  48. Cytokine-induced neutrophil-derived interleukin-8.
    Am J Pathol. 1992 Aug;141(2):397-407 PMID: 1497091
  49. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines.
    Crit Rev Immunol. 1992;12(1-2):17-46 PMID: 1418604
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118734
Published
1996-06-15
Pages
2792-802
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507372
Subset
IM
Grants
NHLBI NIH HHS · 1P-50HL-46487 · United States
NCI NIH HHS · CA-66180 · United States
NHLBI NIH HHS · HL-50057 · United States
External Links
PubMed source DOI: 10.1172/JCI118734 PMC Full Text View journal details
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