Immune Netw.  2003 Mar;3(1):53-60. 10.4110/in.2003.3.1.53.

Production of IFN-gamma by TNF-alpha in Macrophages from Tumor Micro Environment; Significance in Angiogenic Switch Control

• Pyo SN
• Baek S
• Kwak JD
• Park DS
• Joe SJ
• Lee HA

• KMID: 2167971
• DOI: http://doi.org/10.4110/in.2003.3.1.53

Abstract

BACKGROUND
The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-alpha. Recently, macrophage also can produce the INF-gamma that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-alpha can modulate the INF-gamma production in the macrophages from tumor environment as a part of tumor angiogenic switch. METHODS: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. Mac1(+) -macrophages were purified using magnetic bead (MACs(TM); Milteny Biotech, Germany) and cultured with various concentrations of TNF-alpha for various time points at 37degreeC. The supernatants were analyzed for IFN-gamma or VEGF by ELISA kit (Endogen, Woburn, MA). RESULTS: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-alpha to produce INF-gamma. However, the cells from tumor environment produced IFN-gamma as well as VEGF and upregulated by the addition of LPS or TNF-alpha. RT-PCR analysis revealed the external TNF-alpha-induced IFN-gamma gene expression in the macrophages from tumor environment. CONCLUSION: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-alpha might be a key cytokine in tumor angiogenic switch.

Keyword

Tumor micro-environment; angiogenic switch control; macrophages; TNF-alpha; IFN-gamma

MeSH Terms

Animals
Cell Line
Cytokines
Enzyme-Linked Immunosorbent Assay
Gene Expression
Intercellular Signaling Peptides and Proteins
Macrophages*
Melanoma
Mice
Peritoneal Cavity
Tumor Necrosis Factor-alpha*
Vascular Endothelial Growth Factor A
Cytokines
Intercellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A