Fig. 1

Summary of the intercellular crosstalk between cancer cells and CAFs via EVs. The interplay between cancer cells and cancer-associated fibroblasts (CAFs) generates a unique tumour microenvironment (TME) that supports cancer progression. Cancer cells utilize EVs to modify surrounding cells within the tumour microenvironment. Cancer cells secrete various bioactive molecules in EVs, which are transferred into the surrounding fibroblasts and CAFs; such molecules include transforming growth factor-beta (TGF-β), ITGB4, p53, mRNAs and miRNAs (Table 1). These cancer-derived EVs confer specific phenotypes, such as mitophagy and glycolysis, myofibroblast features, matrix remodelling, and inflammatory gene expression (blue arrows), to support cancer progressions (broken arrows, the functions for cancer progression) (Table 1). Cancer-derived EVs also induce distinct CAF subtypes and contribute to the heterogeneity of CAFs. On the other hand, to support cancer progression, CAFs utilize EVs to transfer various functional molecules, such as CD81, CD9, FAP, miRNAs, lncRNAs, transposable RNAs and metabolites. These molecules confer aggressive phenotypes on cancer cells (red arrows). However, some molecules are downregulated in CAFs and thus their transfer to cancer cells is prevented (Table 2). Interestingly, specific CAF subtype-derived EVs are also involved in cancer progression, suggesting that EV content may differ among CAF subtypes