Visualization of Cancer Cell-Derived Exosome-Induced Fibroblast Phenotypic Transformation

Abstract

Fibroblast phenotypic transformation plays a crucial role in tumorigenesis. Tumor cell-derived exosome-mediated fibroblast phenotypic transformation has been commonly studied. However, there is still no direct evidence that the process of tumor cell-derived exosomes induces the transformation of fibroblasts into cancer-associated fibroblasts (CAFs). Herein, exosomal miRNAs were used as a target to track the invasion of cancer cell-derived exosomes into normal fibroblasts, and FAP mRNA, a CAF biomarker, further to trace the effect of exosomes on recipient cells. Two DNA tetrahedral sensors were developed based on a hybrid chain reaction signal amplification strategy and fluorescence resonance energy transfer mechanism. Both sensors showed high sensitivity and good selectivity, with detection limits of 4.94 and 6.61 pM for miR-1247-3p and FAP mRNA, respectively. Moreover, two sensors allowed us to image living cell postinvasion of tumor-derived exosomes, facilitating visual monitoring of fibroblast phenotype transformation and uncovering new perspectives on cancer metastasis development.