Fig. 2

The role of tumour-derived sEVs (TDsEVs) in the formation and progression of cancer. TDsEVs participate in tumour microenvironment (TME) remodelling, angiogenesis, invasion, metastasis and drug resistance. TDsEVs promote epithelial-mesenchymal transition (EMT) process and convert other cells such as mesenchymal stromal cells (MSCs), fibroblasts, epithelial cells, endothelial cells into cancer-associated fibroblasts (CAFs), which in turn release sEVs to promote the malignance of tumour cells. Growth-promoting and pro-angiogenic factors such as VEGF, FGF, and TGF-β carried by TDsEVs promote proliferation of epithelial cells and blood vessels. By activating anti-apoptotic pathways, inducing drug efflux, and suppressing immune cells, TDsEVs mediate the escape to cytotoxic killing. Cancer stem cells (CSCs) release sEVs to maintain the stemness properties of the TME and further promote drug resistance. TDsEVs remodel the extracellular matrix (ECM) and the TME through intracellular communication and multiple molecules. Additionally, miRNAs carried by TDsEVs destroy tight junctions between epithelial cells and promote vascular leakiness, while other molecules such as integrins participate in the formation of a premetastatic niche (PMN), thus promoting the metastasis of migratory cancer cells