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• W2947024711 abstract "Abstract The tumor microenvironment offers favorable conditions for tumor progression, and activated fibroblasts, known as cancer‐associated fibroblasts, play a pivotal role. TP 53‐deficient cancer cells are known to induce strong fibroblast activation. We aimed to elucidate the oncogenic role of exosomes derived from TP 53‐deficient colon cancer cells in fibroblast proliferation and tumor growth. Cancer cell‐derived exosomes ( CDE s) were isolated from the conditioned media of cancer cells using a sequential ultracentrifugation method. The effects of exosomes on tumor growth were evaluated using human cell lines ( TP 53 ‐WT colon cancer, HCT 116; TP 53 ‐mutant colon cancer, HT 29; and fibroblasts, CCD ‐18Co and WI ‐38) and an immune‐deficient nude mouse xenograft model. HCT 116 ( HCT 116 sh p53 ) cells deficient in TP 53 accelerated cocultured fibroblast proliferation compared to TP 53 ‐WT HCT 116 ( HCT 116 sh control ) cells in vitro. Exosomes from HCT 116 sh p53 cells suppressed TP 53 expression of fibroblasts and promoted their proliferation. Xenografts of HCT 116 sh p53 cells grew significantly faster than those of HCT 116 sh control cells in the presence of co‐injected fibroblasts, but this difference was diminished by CDE inhibition. Microarray analysis identified upregulation of several micro RNA s (miR‐1249‐5p, miR‐6737‐5p, and miR‐6819‐5p) in TP 53‐deficient CDE s, which were functionally proven to suppress TP 53 expression in fibroblasts. Exosomes derived from TP 53 ‐mutant HT 29 cells also suppressed TP 53 expression in fibroblasts and accelerated their growth. The proliferative effect of HT 29 on cocultured fibroblasts was diminished by inhibition of these mi RNA s in fibroblasts. Our results suggest that CDE s play a pivotal role in tumor progression by fibroblast modification. Cancer cell‐derived exosomes might, therefore, represent a novel therapeutic target in colon cancer." @default.
• W2947024711 created "2019-06-07" @default.
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• W2947024711 date "2019-07-09" @default.
• W2947024711 modified "2023-10-12" @default.
• W2947024711 title "Exosomal micro<scp>RNA</scp>s derived from colon cancer cells promote tumor progression by suppressing fibroblast <i><scp>TP</scp>53</i> expression" @default.
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• W2947024711 doi "https://doi.org/10.1111/cas.14084" @default.
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