Authors:

David Arteaga

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About Paper:

KRAS, a gene essential for regulating a multitude of cell autonomous processes involved in cell growth and survival, is the most mutated RAS isoform found in non-small cell lung cancer (NSCLC). Recent studies have highlighted the effects of aberrant KRAS signaling in promoting a pro-tumorigenic microenvironment characterized by increased tumorigenesis and immune evasion. Extracellular vesicles (EVs) in cancer are key mediators of intercellular communication and have been shown to facilitate malignant transformations of healthy cells and regulate immune responses. However, the mechanisms by which EVs shape the microenvironment of KRAS-mutant tumors remains understudied and unraveling these mechanisms could improve patient outcomes. In this study, we evaluated EVs isolated from mutant-KRAS NSCLC on their ability to drive migration of non-tumorigenic lung epithelial cells and their effects on T-cell proliferation with the use of transwell migration assays, T-cell proliferation experiments, and flow-cytometry. Our results revealed non- tumorigenic lung epithelial cells co-cultured with EVs derived from mutant-KRAS expressing cells had a higher rate of migration and blocking KRAS signaling disrupted this pro-migratory phenotype elicited by the EVs. Furthermore, T-cells co-cultured with EVs derived from mutant-KRAS expressing cells exhibited decreased proliferation. These results suggest mutant KRAS signaling could play a novel role in promoting the tumor microenvironment by regulating extracellular vesicles to elicit pro-migratory phenotypes in healthy recipient cells and modulate immunosuppression to promote further tumorigenesis of KRAS-mutant non-small cell lung cancer.

Source:

Purdue University / 2023

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No topics listed

Co-authors:

David Arteaga