Tumor microenvironment-derived exosomes-assisted single-cell-derived tumor-sphere formation and drug-resistance by a microfluidic system

Abstract

Without changing the cell biological characteristics, single-cell-derived tumor-sphere (SCDTS) is encouraged to be applied in exploring tumor stem-like cells (TSCs). Whereas, tumor microenvironment simulation is required for promoting SCDTS formation as that TSCs are under rigid regulation from their microenvironment. Tumor microenvironment-derived exosomes (TMDEs) have been employed as a potential approach for simulating tumor microenvironment. Herein, we developed a microfluidic system for TMDEs isolation, the analysis of TMDEs effect on SCDTS formation and the SCDTS drug-resistance. As a proof of concept, the exosomes of primary breast cancer associated fibroblasts (CAFs) were isolated, and the effects of CAF exosomes on SCDTS formation of single breast cells (MCF-7 and MDA-MB-231) with different sizes and deformations were perceived. Then, the SCDTS co-cultured with paclitaxel were adopted for anticancer drug assessment. Results showed that CAF exosomes could be isolated with a simple method, and promote the formation rate and size of SCDTS. Moreover, the smaller and/or more deformable TSCs could be more sensitive to CAF exosomes and more resistant to chemotherapeutics than the larger and/or lesser deformable TSC. Our device supplies a novel modality for promoting SCDTS formation and TSC heterogeneity study.