Fig. 2

The functional network of exosomes in the CCA microenvironment. Exosomes secreted by cancer cells facilitate tumor angiogenesis by transferring Circ-CCAC1 to endothelial cells. Cancer cell-derived exosomes induce BMSCs to differentiate into CAFs to promote tumor stroma formation, and normal fibroblasts can also be activated through their miRNA cargoes, like miR-34c. Other RNAs cargoes, such as Circ-0000284 can promote tumor development by inducing a malignant transformation of normal cholangiocytes, while miR-30e-enriched exosomes inhibit tumor progression via suppressing EMT. Similarly, exosomes derived from Hepatic stellate cells exert an anti-tumor effect by transferring miR-195. Certain protein components in exosomes can also promote tumor proliferation and metastasis, like FZD10. CIKs absorb exosomes to promote tumor immune escape by reducing the secretion of TNF-α and perforin