Journal
STEM CELLS INTERNATIONAL
Volume 2022, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2022/3805013
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Funding
- Natural Science Foundation of Chongqing in China
- National Natural Science Foundation of China
- [cstc2021jcyj-bshX0073]
- [81972851]
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The study found that tumor cell-derived extracellular vesicles (T-EVs) can induce the transformation of normal lung fibroblasts (NFs) into cancer-associated fibroblasts (CAFs), and promote the metastasis of lung cancer cells by regulating inflammation levels, cell proliferation, invasion, and migration.
Human lung cancer (LC) cells A549/H358, normal lung epithelial cells BEAS-2B, and lung normal fibroblasts (NFs) were cultured, followed by transfection of H358 cells with HOTAIR shRNA. Extracellular vesicles (EVs) extracted from H358 cells were identified. The internalization of Dil-labeled-EVs by NFs was tested, and protein levels of cancer-associated fibroblast (CAF) surface markers, inflammatory cytokines, cell proliferation, invasion, and migration, and lncRNA HOTAIR levels were determined. A549 cells were cultured in an H358-EVs-treated conditioned medium of NFs (NFCM), followed by intravenous injection of A549 cells into nude mice. The lesions and Ki-67-positive cells in lung tissues were measured. The results showed that tumor cell-derived EVs (T-EVs) motivated the transformation of NFs into CAFs. Specifically, EVs can be internalized by NFs, and the protein levels of CAF surface markers and inflammation levels were elevated in H358-EVs-treated NFs. The proliferation, invasion, and migration of A549 cells cultured in T-EVs-treated NFCM were increased. H358-EVs carried HOTAIR into NFs and promoted the transformation of NFs into CAFs. Inhibition of HOTAIR partially reversed the promoting effect of H358-EVs on the transformation of NFs into CAFs and invasion and migration of LC cells. T-EVs promoted metastasis of LC in vivo by transforming NFs into CAFs.
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