Colorectal Cancer Cells-Fibroblasts Interaction Regulates Connexin43 Expression In Colorectal Carcinoma

Background Colorectal cancer is one of the most malignant tumors in the world, and has been threatening people's health seriously.Therefore,it is of significance to investigate its pathogenesis,which can improve our diagnosis and treatment of the cancer.Tumor micro-environment plays an important role in the growth,invasion and metastasis of tumor.Activated fibroblasts,also known as myofibroblasts or CAFs (cancer-associated fibroblasts),which expressα-SMA,the marker of CAFs,is the most abundant cells in the tumor micro-environment.Some reseachers have found that CAFs can promote the proliferation of tumor cells.Cell-cell communication has two ways:direct interaction and indirect interaction. Direct interaction happens mainly through intercellular gap junction,while indirect interaction mainly through cytokines.The gap junction intercellular communication (GJIC)plays a vital role in the development and maintenance of organs.Connexin43, as one of the intercellular connection proteins,has decreased expression in many cancer cells.So,restoring the GJIC could suppress tumor growth and transformation, and will open a new way for tumor treatment.Objective We have found that colon cancer cells - fibroblasts interaction can induce the expression of CX43,so our further study is to find which cells do express CX43, and which type of gap junction the interaction restores,and to investigate the mechanism.Methods1.Colorectal cell line SW620 cells was co-cultured with or without fibroblasts HSF cells for 24,48 and 72h,respectively,the expression of CX43 andα-SMA in the cells were measured by IHC,IF and Western-blot analysis.2.SW620 cells were cultured in HSF-conditioned-medium treated by TGF-β1 for 72h,and CX43 expression was detected by IHC.Results1.SW620 cells cocultured with HSF cells appeared to express CX43.2.HSF cells cocultured with SW620 cells express moreα-SMA than that cocultured without SW620 cells.3.TGF-β1 inducedα-SMA expression of HSF cells.4.SW620 cells expressed CX43 in HSF- conditioned-medium treated by TGF-β1.Conclusion1.SW620-HSF interaction can induce CX43 expression,restoring GJIC ONLY in SW620 cells.2.SW620-HSF interaction can activize HSF cells to myofibroblasts.3.Myofibroblasts,NOT HSF cells induce CX43 expression in SW620 cells.4.TGF-β1 may contribute to CX43 expression in the SW620-HSF interaction.