The role of cancer-associated fibroblasts in renal cell carcinoma. An example of tumor modulation through tumor/non-tumor cell interactions

Cancer-associated fibroblasts (CAF) are a cellular compartment of the tumor microenvironment (TME) with critical roles in tumor development. Fibroblast activation protein-α (FAP) is one of the proteins expressed by CAF and its immunohistochemical detection in routine practice is associated with tumor aggressiveness and shorter patient survival. For these reasons, FAP seems a good prognostic marker in many malignant neoplasms, including renal cell carcinoma (RCC). The start point of this Perspective paper is to review the role of CAF in the modulation of renal cell carcinoma evolution. In this sense, CAF have demonstrated to develop important protumor and/or antitumor activities. This apparent paradox suggests that some type of temporally or spatially-related specialization is present in this cellular compartment during tumor evolution. The end point is to remark that tumor/non-tumor cell interactions, in particular the symbiotic tumor/CAF connections, are permanent and ever-changing crucial phenomena along tumor lifetime. Interestingly, these interactions may be responsible of many therapeutic failures.