BSBM-22 CHARACTERIZATION OF CIRCULATORY SHEAR STRESS-INDUCED MOLECULAR CHANGES IN LUNG ADENOCARCINOMA CELLS AND IMPLICATIONS IN BRAIN METASTASIS
نویسندگان
چکیده
Abstract INTRODUCTION Lung cancer is the most common tumor to metastasize brain, as 40% of patients develop brain metastasis (BM). Once diagnosed, survival only 6.5-10 months. A potential target prevent BM circulating cells (CTCs). The mechanisms that mediate a CTCs adaptation harsh environment circulation and have not been elucidated. We demonstrated primary lung (LCCs) subjected increased migration across endothelial cell monolayers, side population, decrease in rodents when injected intracardially vs plated controls. METHODS engineered microfluidic device capable subjecting prolonged circulatory shear stress (CSS) allows isolation/modeling CTC-like cells. Primary LCCs (A549, H1563) were circulation, suspension, or (2D) for 72h At this time point, collected, total mRNA was extracted. Samples submitted RNA sequencing. Weighted gene co-expression network analysis (WCGNA) Ingenuity Pathway Analysis performed. (FC >2 p-value <0.05). RESULTS Transcriptomic indicates CSS activate specific networks involved survival, migration, invasion, adhesion cells, cytoskeletal reorganization (z-score: >2, p-value: 0.05). Canonical pathways included ILK-signaling Xenobiotic Metabolism. exposed had expression multidrug resistance pumps ABCC2, ABCF2 (P:<0.001), population on flow cytometry (P: top differentially expressed genes (MMP1, ANGPTL4, CEMIP) angiogenesis, pre-metastatic niche (PMN) formation BM. CONCLUSION survive associated with chemoresistance compared 2D Targeting preparation PMN may be useful preventing
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ژورنال
عنوان ژورنال: Neuro-oncology advances
سال: 2023
ISSN: ['2632-2498']
DOI: https://doi.org/10.1093/noajnl/vdad070.018