Radiation induces epithelial-mesenchymal transition in colorectal cancer cells
Radiation induces epithelial-mesenchymal transition in colorectal cancer cells
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DOI：
10.3892/or.2011.1485
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
--
作者：
Kawamoto, Aya;Yokoe, Takeshi;Kusunoki, Masato
放射治疗仍然是晚期直肠癌患者辅助治疗的主要方法。然而，辐射对恶性过程的影响尚待澄清。本研究的目的是评估辐射对结直肠癌（CRC）细胞的生物学效应，特别是上皮间质转化（EMT），这是癌症侵袭和转移过程中经常激活的关键发育程序。我们研究了辐射对两种结直肠癌细胞系CaR 1和DLD 1的影响，评估了细胞形态、运动性、迁移和侵袭能力。使用RT-PCR、Western印迹和免疫荧光染色在对照和辐照细胞中确定与EMT相关的分子的表达。我们还使用实时RT-PCR检测了放化疗前后EMT相关分子的表达。因此，我们研究了26例直肠癌患者，他们接受术前放化疗，然后进行根治性手术。此外，我们还研究了疾病复发与一些蛋白质表达之间的关系。辐射导致CRC细胞经历EMT的表型变化特征：梭形细胞形状、极性丧失、细胞间分离和伪足形成。辐射增强细胞迁移和侵袭力。在辐射的CRC细胞中，观察到与EMT一致的分子变化。在临床样本中，我们观察到与EMT一致的分子变化，并且这些变化在复发性疾病患者中显著增强。这些结果表明，辐射诱导的恶性表型的改变与大肠癌细胞中的EMT一致。
Radiotherapy remains a major approach to adjuvant therapy for patients with advanced rectal cancer. Nevertheless, the effects of radiation on malignant processes have yet to be clarified. The aim of this study was to assess the biological effects of radiation on colorectal cancer (CRC) cells with special reference to epithelial-mesenchymal transition (EMT), a key developmental program often activated during cancer invasion and metastasis. We investigated the effect of radiation on two colorectal cancer cell lines, CaR1 and DLD1, assessing cell morphology, motility, migration and invasive ability. Expression of molecules associated with EMT was determined using RT-PCR, Western blotting, and immunofluorescence staining in control and irradiated cells. We also used real-time RT-PCR to examine the expression of molecules associated with EMT before and after chemoradiotherapy. Thus, we studied 26 rectal cancer patients who received preoperative chemoradiotherapy followed by radical surgery. In addition, we examined the relationship between disease recurrence and the expression of a number of proteins. Irradiation caused CRC cells to undergo phenotypic changes characteristic of EMT: spindle-cell shape, loss of polarity, intercellular separation and pseudopodia formation. Irradiation enhanced cell migration and invasiveness. In irradiated CRC cells, molecular changes consistent with EMT were observed. In clinical samples, we observed molecular changes consistent with EMT, and those changes were significantly enhanced in patients with recurring disease. These results indicate that irradiation induces an alteration to a malignant phenotype consistent with EMT in colorectal cancer cells.