Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Oncol Rep. 2012 Jan;27(1):51-7. doi: 10.3892/or.2011.1485. Epub 2011 Oct 3.
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.
放疗仍然是治疗晚期直肠癌患者的主要辅助治疗方法。然而，辐射对恶性过程的影响尚未得到阐明。本研究旨在评估辐射对结直肠癌（CRC）细胞的生物学效应，特别关注上皮-间充质转化（EMT），这是癌症侵袭和转移过程中经常激活的关键发育程序。我们研究了两种结直肠癌细胞系 CaR1 和 DLD1 对辐射的反应，评估细胞形态、运动性、迁移和侵袭能力。在对照和照射细胞中，使用 RT-PCR、Western blot 和免疫荧光染色来确定与 EMT 相关的分子的表达。我们还使用实时 RT-PCR 来检测放化疗前后与 EMT 相关的分子的表达。因此，我们研究了 26 例接受术前放化疗后行根治性手术的直肠癌患者。此外，我们还检查了疾病复发与多种蛋白表达之间的关系。照射导致 CRC 细胞发生 EMT 的特征性表型变化：纺锤形细胞形状、极性丧失、细胞间分离和伪足形成。照射增强了细胞迁移和侵袭能力。在照射的 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，并且在复发疾病患者中这些变化显著增强。这些结果表明，照射诱导结直肠癌细胞发生与 EMT 一致的恶性表型改变。
