ABSTRACT
@#The three-dimensional cell model cultures different types of cells in vitro. By means of special materials or carriers, the cells can grow, migrate and differentiate in a three-dimensional environment. The three-dimensional cell model provides the cells with an in vitro environment that is close to in vivo, making the gene expression and signal exchange of the cells more physiologically relevant. This paper starts with the concept and classification of three-dimensional cell model, then summarizes the applications and progresses of three-dimensional cell model in tumor micro-environment, cancer metastasis and anti-tumor drug development in recent years. Based on the current shortcomings of the three-dimensional cell model, this paper presents the assumptions and prospects for the application of three-dimensional cell model in tumor therapy.
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.