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Maleki, Saeideh

University of British Columbia

Lung adenocarcinoma (LUAD) is the most frequent subtype of non-small cell lung cancer and is the leading cause of cancer death worldwide. Due to the late stage of diagnosis, five-year survival rate of LUAD remains dismally low at approximately 15%. A better understanding of the molecular mechanisms that occur in the cells of the tumor and surrounding microenvironment will aid in identifying new therapeutic targets and thus improve overall survival. Extracellular vesicles (EVs) derived from cancer cells are one of the main facilitators of communication with the tumor microenvironment (TME). Fibroblasts of the TME uptake secreted EVs and differentiate into cancer-associated fibroblasts (CAFs), leading to tumor growth and progression. Herein, differentially expressed genes in lung fibroblasts co-cultured with LUAD EVs were identified and compared with TGFβ-treated fibroblasts. Additionally, different CAF subtypes as well as signaling pathways activated in each treatment group were characterized. While the majority of differentially expressed genes between the EV-treated and TGFβ-treated groups were similar, those co-cultured with LUAD EVs showed enrichment of inflammatory CAFs and were upregulated in several pathways including NF-κB, IL2, IL-6, IL17 and COMPLEMENT. Fibroblasts co-cultured with TGFβ were dominant in developmental CAFs and shown upregulation in Wnt/β catenin signaling pathway. Together, this data provides a comprehensive analysis of gene expression profiles of LUAD EV-treated fibroblasts and their downstream pathways through which they communicate with the other cells in the TME.

Text

2022-07-13

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/82128

Interdisciplinary Oncology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/