Fig. 5: The hypoxic sEV signature is derived from lung cells that have undergone EMT.

a GSEA identified the hallmark epithelial-to-mesenchymal transition gene set was significantly associated with sEVs derived from hypoxic SKMES1 cells. b Oncogenically induced EMT in mesenchymal 30KTp53/KRAS/LKB1 and H358ZEB1 cells was demonstrated by loss of E-cadherin and gain of vimentin expression assessed by flow cytometry, whereas MET was induced in CALU1 cells through knockdown of ZEB1 (CALU1shZEB1) resulting in the gain of E-cadherin and loss of vimentin expression. c ELISA of MAC2BP, PSMA2, THBS1 and TNC demonstrates that EMT induces an increase of all four signature proteins in sEVs (±SEM; n = 3). d Conversely, when MET is induced in CALU1 cells the abundance of all four signature proteins is significantly reduced (±SEM; n = 3 independent replicates). *p < 0.05, **p < 0.01 ***p < 0.001.