The Mechanism by Which CAFs Maintain the Tumor Cell Stemness to Promote Tumor Drug Resistance

Cancer fibroblasts (CAFs) are the most abundant stromal cells in the solid tumor microenvironment (TME), many different CAF subtypes regulate the TME directly or indirectly. CAFs are an important cell population that promotes tumor cell stemness and maintains the function of cancer stem cells (CSCs). CSC is a kind of special cells that have the characteristics to continue forming some new tumor cells. They play an important role in tumor recurrence and drug resistance. They are the important factors that affect the effectiveness of cancer treatment. At present, the effectual methods that directly target the tumor stem cells are still exploring, but the CAFs can affect the proliferation and growth of CSCs through direct contact between cells and secretion of factors to promote signal pathways, thereby providing a suitable microenvironment for CSCs. Some CAF subtypes have been identified now, but not all, and the mechanisms by which CAFs affect tumor progression still need to be researched. This review analyzes the different sources of CAFs, the role of secreted factors in promoting cancer stemness and drug resistance, also about the regulatory and remodeling role of CAFs in ECM. To summarize how to deal with the cancer-promoting effect of CAFs, thereby reducing their influence on stemness and drug resistance. Therefore, to review how CAFs promote tumor cell stemness to enhance their drug resistance and discuss and analyze the therapy with CAFs, to develop therapy strategies based on the origin of CAFs and the mechanism of CAFs promoting cancer.