Crosstalk between Exosomes and CAFs During Tumorigenesis, Exosome-derived Biomarkers, and Exosome-mediated Drug Delivery

Cancer-Associated Fibroblasts (CAFs) originate from the activation of fibroblasts in the Tumor Microenvironment (TME) during tumorigenesis, resulting in the promotion of tumor growth, metabolism, and metastasis. Exosomes, which can locally or remotely transfer miRNAs, lncRNAs, proteins, metabolites, and other substances to other cells, have a size and range distribution of 30 to 150 nm and have been described as new particles that mediate communication among neighboring and/or distant cells. Exosomes have regulatory roles in the tumor microenvironment that are different from those in the tumor cells, including mediating the regulation of tumor progression, delivery of miRNAs involved in reprogramming Normal Fibroblasts (NFs) into CAFs, and the modulation of tumor initiation and metastasis. Exosomes can be useful biomarkers of the tumor microenvironment and for the therapy and diagnosis of different diseases. Relevant interactions with cancer cells reprogram NFs into CAFs or allow cell-to-cell communication between CAFs and cancer cells. Several researchers have started exploring the precise molecular mechanisms related to exosome secretion, uptake, composition, and corresponding functions of their "cargo." However, little is known about the processes by which exosomes affect cancer behavior and their potential use as diagnostic biomarkers for cancer treatment. Therefore, the crosstalk between CAFs and exosomes during tumorigenesis and the effects of exosomes as biomarkers and drug carriers for therapy are discussed in this review.