Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schaider, H; Oka, M; Bogenrieder, T; Nesbit, M; Satyamoorthy, K; Berking, C; Matsushima, K; Herlyn, M.
Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8.
Int J Cancer. 2003; 103(3):335-343
Doi: 10.1002/ijc.10775
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Schaider Helmut
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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/10(5) 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenoviridae -
- Animals -
- Chemotaxis, Leukocyte - physiology
- Cytotoxicity, Immunologic - physiology
- Disease Progression - physiology
- Endothelial Growth Factors - metabolism
- Humans - metabolism
- Immunoenzyme Techniques - metabolism
- Intercellular Signaling Peptides and Proteins - metabolism
- Interleukin-8 - physiology
- Lymphokines - metabolism
- Melanoma - metabolism
- Mice - metabolism
- Mice, Nude - metabolism
- Neutrophils - physiology
- Skin Neoplasms - metabolism
- Transfection - metabolism
- Tumor Cells, Cultured - metabolism
- Vascular Endothelial Growth Factor A - metabolism
- Vascular Endothelial Growth Factors - metabolism
- Find related publications in this database (Keywords)
- IL-8
- melanoma
- adenoviral vector
- neutrophil
- vascular
- endothelial growth factor
- RB6-8C5