Autologous tumor‑derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and cellular respiration in gastric cancer cells

自体肿瘤衍生的微泡影响基因表达谱并增强胃癌细胞的致瘤趋化潜力、信号转导和细胞呼吸

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作者:Rafal Szatanek, Kazimierz Weglarczyk, Malgorzata Stec, Jaroslaw Baran, Magdalena Parlinska-Wojtan, Maciej Siedlar, Monika Baj-Krzyworzeka

Abstract

Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, intercellular signaling and cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and cellular respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on cellular respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.

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