This proved that TGF-β has antagonism with IFN-γ, can resume the growth of tumor cells, migration, and invasion;
it can also lead to the situation wherein IFN-γ reduces the activity of the tumor cells’ MMPs. In this situation, the tumor cells restored growth and invasion, and avoided the inhibition of IFN-γ. The Wnt inhibitor validation experiment in vivo also presented a similar effect on the tumor by IFN-γ injection. The level of TGF-β also increased significantly in the inhibition missing phase. Furthermore, the activities of MMP-2 and MMP-9 were also enhanced in the inhibition missing phase as compared to those in the inhibition phase. TGF-β is an important mediator of tumor progression, which likewise regulates cell proliferation, Dibutyryl-cAMP migration, and invasion; it is an important cytokine involved in a variety of biological processes [35, 36]. We detected VEGF-a, bFGF, and other cytokines both in the serum and tumor tissue. However, www.selleckchem.com/products/gm6001.html only the expression of TGF-β up-regulated in the “”inhibition missing phase,”" and was positively correlated to an increase in tumor size. The in vitro data proved that TGF-β can confront IFN-γ so that the tumor cells can restore proliferation and migration, and that it has the ability to resume invasion and the activity of the MMPs. The validation data in vivo also showed
similar effect and phenotype. The IHC data also support this conclusion, as well as point out that Col IV is likewise regulated by the TGF-β/IFN-γ level. In conclusion, the study has proven that when the wound and the tumor exist at the same time, there will be a new balance
between TGF-β and IFN-γ. The wound, through the secretion of IFN-γ, interferes with the growth of the tumor cells and inhibits the tumor for a short period. Some tumor cells, through unknown mechanisms, use TGF-β against the IFN-γ effect in the restoration of tumor proliferation, invasion, and migration. As for the source of TGF-β, we speculated that the tumor cells mainly came from inflammatory factors such as IFN-γ adaptability to up-regulated expression, or were derived from the interaction between the tumor cells and the stromal cells. This needs further research to be conclusive. However, this study has proven that at least, in the interaction between tumor and inflammation by wounds, the existence of a new balance between TGF-β and IFN-γ not only contributes Adenosine triphosphate to the understanding of how tumor cells adapt to the inflammatory factor, but also provides a new basis to analyze the effects of the inflammatory process on tumors. This study also provides a reference to tumor surgery, especially in post-operative residual tumor assessment. Acknowledgements This work was partly supported by a grant from the National Nature Science Foundation of China (No. 30370554 and No. 30830049). References 1. Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001, 357: 539–545.CrossRefPubMed 2.