IL-6 Released By Macrophage Promotes Migration And Invasion Of Colon Cancer Cells Via WNT/?-catenin Signaling Pathway

Macrophages play an irreplaceable role in innate immunity. They distribute widely in tumor tissues and involve in the progression of tumors by secreting a variety of cytokines. As a cytokine that macrophage secretes, IL-6 is involved in the progression of tumors, including the invasion and metastasis via kinds of signaling pathways. This study is to explore the actions and mechanisms of macrophage and IL-6 in the invasion and metastasis of human colon cancer. The main contents and results of this study are listed as below:1. Macrophage and IL-6 are associated with the progression of colon cancerThe tissue biopsies of normal colon, primary colon tumor and its lymph node metastasis were observed with the method of immunohistochemistry. The results showed that CD68+ macrophages were more frequent in the primary colon tumor than normal colon tissue, and more in the metastatic lymph node than the primary tumor, the expression of IL-6 in the above biopsies also showed the same trend. The observation suggested that the progression of colon cancer may be associated with the infiltrated microphages and their produced IL-6.2. The IL-6 secreted by macrophages promotes the migration and invasion of human colon cancer cell line cultured in vitroThe supernatants of macrophages containing high-level IL-6 were used to treat a human colon cancer cell line SW48. The supernatant-treated SW48 cells shows more migration and invasion ability, as detected via wound-healing, Transwell tests. The promotion of the SW48 migration and invasion was blocked while the IL-6 was neutralized, demonstrating that the macrophage-secreted IL-6 could apparently accelerate the migration and invasion of colon cancer cell line.3. The WNT/?-catenin signaling pathway is involved in promotion of the SW48 migration and invasion by IL-6Vimentin and ?-catentin are the molecules associated with tumor migration and invasion. The supernatant-treated SW48 cells expressed more vimentin and ?-catentin observed with Western Blot, especially in the 24 th hour after the co-culture. Inversely, both the Vimentin and ?-catentin decreased after IL-6 was neutralized. These observations suggested that the IL-6 released by macrophage promote the SW48 migration and invasion via WNT/?-catenin signaling pathway. Meanwhile, p-STAT3 and p-ERK expression were also increased in the supernatant-treated SW48 cells, suggesting that IL-6 may promote the SW48 migration and invasion via the IL-6/IL-6R signaling pathway.This study explored the actions and mechanisms of colon cancer progression promoted by macrophage-secreted IL-6, with the tissue biopsies and human colon cancer cell SW48 tests in vitro. The results showed that macrophage-secreted IL-6 promotes migration and invasion of colon cancer cells via WNT/?-catenin signaling pathway. Our observations would provide an experimental basis to better understanding of colon cancer progression and development of the tumor immunotherapy.