Extracellular vesicles released by NSCLC cells drive invasion and permeability in non-tumorigenic lung epithelial cells

Extracellular vesicles (EVs) released from non-small cell lung cancer (NSCLC) cells are known to promote cancer progression. However, it remains unclear how EVs from various NSCLC cells differ in their secretion profile and their ability to promote phenotypic changes in non-tumorigenic cells. Researchers at Purdue University performed a comparative analysis of EV release from non-tumorigenic cells (HBEC/BEAS-2B) and several NSCLC cell lines (A549, H460, H358, SKMES, and Calu6) and evaluated the potential impact of NSCLC EVs, including EV-encapsulated RNA (EV-RNA), in driving invasion and epithelial barrier impairment in HBEC/BEAS-2B cells.

Secretion analysis revealed that cancer cells vary in their secretion level, with some cell lines having relatively low secretion rates. Differential uptake of NSCLC EVs was also observed, with uptake of A549 and SKMES EVs being the highest. Phenotypically, EVs derived from Calu6 and H358 cells significantly enhanced invasion, disrupted an epithelial barrier, and increased barrier permeability through downregulation of E-cadherin and ZO-1. EV-RNA was a key contributing factor in mediating these phenotypes. More nuanced analysis suggests a potential correlation between the aggressiveness of NSCLC subtypes and the ability of their respective EVs to induce cancerous phenotypes.

Overall summary of the study and key findings

Figure 6

(A) Data compiled from all the experiments in the study is summarized in the form of a heatmap. Hierarchical clustering indicates the differences in EV secretion rate, EV uptake, and the potential of various NSCLC EVs and EV-RNA to induce pro-tumorigenic transformations in HBEC/BEAS-2B cells (distance method = euclidean, clustering method = ward.D2). Grey boxes indicate samples that were not tested/evaluated (NT). TEER change in BEAS-2B barriers ranges from positive change (blue) to negative change (orange). (B) Key findings from the study include the following: (1) Biophysical and molecular analysis of EVs determined that the EV secretion rate for some NSCLC cell lines is lower than secretion rates from non-tumorigenic bronchial epithelial cells. It was also determined that EVs from non-tumorigenic cells and NSCLC cells have similar total RNA and total protein content per EV. (2) EVs from the various NSCLC cell types differ in their uptake by non-tumorigenic cells. (3) NSCLC EVs as well as EV-RNA can disrupt a BEAS-2B epithelial barrier and downregulate intercellular junctional complex proteins; (4) NSCLC EVs and EV-RNA can impart an invasive phenotype in non-tumorigenic HBEC and BEAS-2B cells.

Hasan H, Sohal IS, Soto-Vargas Z et al. (2022) Extracellular vesicles released by non-small cell lung cancer cells drive invasion and permeability in non-tumorigenic lung epithelial cells. Sci Rep 12, 972 [article]

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