The Role of Cancer Stem Cell-Derived Exosomes in Cancer Progression

Figure 5

CSC-Exos play a role in the regulation of the tumor microenvironment (TME). Exosomes derived from pancreatic cancer (PaCa) cells are rich of miR-155 and promote the differentiation of fibroblasts into cancer-associated fibroblasts (CAFs) by downregulating the level of TP53INP1 protein in fibroblasts. Proteins carried by CSC-Exos, such as HSP72 and HSP70, target downstream Toll-like receptor 2 (TLR2) to activate myeloid-derived suppressor cells (MDSCs) to promote the formation of the TME. miR-92a loaded in exosomes derived from K562 tumor cells interacts with the proangiogenic protein integrin α5, causing endothelial cell (EC) migration and primitive vascular lumen formation. Breast cancer-derived exosomes contain miR-105, which downregulates the expression of ZO-1 to increase the permeability of tumor blood vessels in the TME. Gastric cancer cell-derived exosomes (GC-Exos) carry TGF-β, which induces human umbilical cord mesenchymal stem cells (hucMSCs) to differentiate into CAFs through the TGF-β/Smad pathway. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) riched in CSC-Exos activate the MAPK signaling pathway of monocytes and inhibit the cleavage of caspases, which contributes to the formation of tumor-associated macrophages (TAMs).