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组织因子对结直肠癌干细胞的影响。

Effect of Tissue Factor on Colorectal Cancer Stem Cells.

作者信息

Clouston Hamish William, Rees Peter Adam, Lamb Rebecca, Duff Sarah Elizabeth, Kirwan Cliona Clare

机构信息

Institute of Cancer Sciences, The University of Manchester, Manchester, U.K.

Manchester University NHS Foundation Trust, Manchester, U.K.

出版信息

Anticancer Res. 2018 May;38(5):2635-2642. doi: 10.21873/anticanres.12505.

Abstract

BACKGROUND/AIM: Tissue factor (TF) expression increases cancer stem cell (CSC) activity in breast and lung cancer. There are ongoing studies focused on targeting CSCs via anti-TF treatment, for breast and lung cancer therapy. Herein, the aim was to determine whether targeting TF could have an anti-CSC therapeutic role in colorectal cancer (CRC).

MATERIALS AND METHODS

Evaluation of colonosphere-forming efficiency (CFE) and aldehyde dehydrogenase (ALDH) expression level was used to quantify CSC activity in two CRC cell lines, after TF knockdown (TFKD) or TF over-expression (TFOE).

RESULTS

TFKD resulted in increased levels of ALDH in SW620 (1.31±0.04-fold, p<0.001) and DLD-1 (1.63±0.14-fold, p=0.04) cells. CFE was increased in SW620 (1.21±0.23% vs. 2.03±0.29%, p=0.01) and DLD-1 (0.41±0.12% vs. 0.68±0.9%, p=0.01) cells. Conversely, TFOE decreased ALDH expression (0.72±0.04-fold, p=0.001) and CFE (0.33±0.05% vs. 0.66±0.14%, p=0.006) in DLD-1, but had no impact on SW620 cells.

CONCLUSION

In the examined CRC cell lines, TF expression was inversely related to CSC activity suggesting that anti-TF therapies may not have a role in CRC treatment.

摘要

背景/目的:组织因子(TF)表达可增强乳腺癌和肺癌中癌症干细胞(CSC)的活性。目前有多项研究聚焦于通过抗TF治疗靶向CSC,用于乳腺癌和肺癌治疗。在此,目的是确定靶向TF在结直肠癌(CRC)中是否具有抗CSC治疗作用。

材料与方法

在两个CRC细胞系中,经TF敲低(TFKD)或TF过表达(TFOE)后,通过评估结肠球形成效率(CFE)和醛脱氢酶(ALDH)表达水平来量化CSC活性。

结果

TFKD导致SW620细胞(1.31±0.04倍,p<0.001)和DLD-1细胞(1.63±0.14倍,p=0.04)中ALDH水平升高。SW620细胞(1.21±0.23%对2.03±0.29%,p=0.01)和DLD-1细胞(0.41±0.12%对0.68±0.9%,p=0.01)的CFE升高。相反,TFOE降低了DLD-1细胞中ALDH的表达(0.72±0.04倍,p=0.001)和CFE(0.33±0.05%对0.66±0.14%,p=0.006),但对SW620细胞无影响。

结论

在所检测的CRC细胞系中,TF表达与CSC活性呈负相关,提示抗TF疗法可能对CRC治疗无效。

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