Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8

Schaider, Helmut, Oka, Masahiro, Bogenrieder, Thomas, Nesbit, Mark, Satyamoorthy, Kapaettu, Berking, Carola, Matsushima, Kouji and Herlyn, Meenhard (2003) Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. International Journal of Cancer, 103 3: 335-343. doi:10.1002/ijc.10775


Author Schaider, Helmut
Oka, Masahiro
Bogenrieder, Thomas
Nesbit, Mark
Satyamoorthy, Kapaettu
Berking, Carola
Matsushima, Kouji
Herlyn, Meenhard
Title Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
1097-0215
Publication date 2003-01-20
Year available 2002
Sub-type Article (original research)
DOI 10.1002/ijc.10775
Open Access Status
Volume 103
Issue 3
Start page 335
End page 343
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Formatted abstract
IL-8 is a strong chemoattractant for neutrophils, and it is constitutively produced by many tumors, including human melanomas. To determine the biologic importance of IL-8 for melanoma cells from primary and metastatic lesions, we transduced selected cell lines constitutively producing low levels of IL-8 with IL-8 cDNA using a replication-deficient adenoviral vector. Nontumorigenic SBcl2 primary melanoma cells formed tumors when transduced with increasing plaque-forming units of IL-8 per cell. However, at high IL-8 transduction levels (100 ng/ml/105 cells in 48 hr), tumor growth was impaired due to massive neutrophil infiltration. A similar biphasic response was observed in WM115 primary melanomas, which are tumorigenic but not metastatic. Depletion of neutrophils with an antibody that blocks the accumulation of granulocytes at the site of inflammation enabled transduced primary melanomas secreting high levels of IL-8 to survive and grow. In contrast, highly tumorigenic and metastatic 451Lu cells showed marked increases in tumor growth and number of metastatic foci in the lungs depending on the expression levels of IL-8. Cytotoxicity assays with isolated neutrophils confirmed the preferential killing of primary over metastatic melanoma cells. SBcl2 cells stimulated by IL-8 to form tumors in immunodeficient mice were induced to produce VEGF, suggesting that the angiogenic response is enhanced due to increased growth factor production. Our results demonstrate that nontumorigenic primary melanomas depend on IL-8 stimulation in vivo for growth and that tumor growth depends on the level of neutrophil infiltration. Metastatic melanomas proliferate in vivo independently of infiltrating neutrophils.
Keyword IL-8
Melanoma
Adenoviral vector
Neutrophil
Vascular endothelial growth factor
RB6-8C5
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article first published online: 12 NOV 2002

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
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