Molecular biological analysis of radiation induced epithelial-mesenchymal transition on cancer stem cell of rectal cancer

辐射诱导直肠癌干细胞上皮-间质转化的分子生物学分析

• 批准号: 22591484
• 负责人: TANAKA Koji
• 金额: $ 3万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591484/
• 关键词: 小腸大腸肛門外科学; 直腸癌; 化学放射線療法; 癌幹細胞; 上皮間葉移行; 大腸癌; 二光子レーザー顕微鏡

We hypothesized that residual cancer cells after chemoradiotherapy (CRT) for rectal cancer have the treatment (CRT)-resistant property and contain putative CSCs, compared with pre-CRT cancer specimens. Furthermore, residual cancer cells which survived CRT may acquire metastatic potential induced by EMT. The expression of CD133, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), glucose transporter 1 (GLUT1), and hypoxia inducible factor-1α (HIF-1α) on residual cancer cells after CRT was associated with cancer recurrence and patient prognosis. The expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) on residual cancer cells after CRT was also associated with cancer recurrence. The expression of CXCR4 and its ligand CXCL12, fibroblast activation protein-α (FAP-α), and stromal cell-derived factor-1 (SDF-1) on the cancer stroma after CRT was also associated with cancer recurrence and patient prognosis. In vitro study, radiation induced EMT in colorectal cancer cells, resulting in the acquisition of invasive and metastatic properties. Neurotrophic receptor tropomyosin related kinase (TrkB) also induced EMT in colorectal cancer cells. TrkB was inversely correlated with E-cadherin, and associated with poor prognosis of colorectal cancer patients. CD133 was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells.

我们假设与前CRT癌标本相比，对直肠癌的化学疗法（CRT）的残留癌细胞具有耐药性（CRT）耐药性，并含有推定的CSC。此外，幸存于CRT的残留癌细胞可能会获得EMT诱导的转移性潜力。在CRT后，CRT上的CD133，CD133，富含亮氨酸重复的G蛋白偶联受体5（LGR5），葡萄糖转运蛋白1（GLUT1）和缺氧诱导因子1α（HIF-1α）在残留癌细胞上的表达与癌症复发和患者预后相关联。 CRT后残留的癌细胞对胸苷酸合酶（TS）和二氢吡啶脱氢酶（DPD）的表达也与癌症复发有关。 CRT后CRT上CXCR4及其配体CXCL12，成纤维细胞激活蛋白-α（FAP-α）和基质细胞衍生因子-1（SDF-1）的表达也与癌症复发和患者提示有关。在体外研究中，辐射在有色癌细胞中诱导EMT，从而获得了侵入性和转移特性。神经营养受体tropomyosin相关激酶（TRKB）也诱导有色癌细胞的EMT。 TRKB与E-钙粘蛋白成反比，并与有色癌症患者的预后不良有关。 CD133以辐射剂量依赖性的方式增加，这是下降辐射延伸细胞数量减少的任务。

项目成果

TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy

• DOI: 10.1002/jso.22123
• 发表时间: 2012-05-01
• 期刊: JOURNAL OF SURGICAL ONCOLOGY
• 影响因子: 2.5
• 作者: Tanaka, Koji;Saigusa, Susumu;Kusunoki, Masato
• 通讯作者: Kusunoki, Masato

The role of cytoreduction for metastatic and recurrent colorectal cancer in the era of multidisciplinary treatments.J Clin Oncol 28, 2010 (suppl; abstre14091)

多学科治疗时代细胞减灭术在转移性和复发性结直肠癌中的作用。J Clin Oncol 28, 2010（增刊；abstre14091）

• 发表时间: 2010
• 作者: K. Tanaka;Y. Inoue;Y. Toiyama;J. Hiro;T. Iwata;S. Saigusa;M. Ohi;C. Miki;S. Kageyama;M. Kusunoki
• 通讯作者: M. Kusunoki

Intravital Three-Dimensional Dynamic Pathology of Experimental Colitis in Living Mice Using Two-Photon Laser Scanning Microscopy

• DOI: 10.1007/s11605-011-1632-5
• 发表时间: 2011-07
• 期刊: Journal of Gastrointestinal Surgery
• 影响因子: 3.2
• 作者: Y. Morimoto;Koji Tanaka;Y. Toiyama;Y. Inoue;T. Araki;K. Uchida;K. Kimura;A. Mizoguchi;M. Kusunoki

Radiation induces epithelial-mesenchymal transition in colorectal cancer cells

• DOI: 10.3892/or.2011.1485
• 发表时间: 2012-01-01
• 期刊: ONCOLOGY REPORTS
• 影响因子: 4.2
• 作者: Kawamoto, Aya;Yokoe, Takeshi;Kusunoki, Masato
• 通讯作者: Kusunoki, Masato

Clinical Significance of CD133 and Hypoxia Inducible Factor-1α Gene Expression in Rectal Cancer after Preoperative Chemoradiotherapy

• DOI: 10.1016/j.clon.2010.09.012
• 发表时间: 2011-06-01
• 期刊: CLINICAL ONCOLOGY
• 影响因子: 3.4
• 作者: Saigusa, S.;Tanaka, K.;Kusunoki, M.
• 通讯作者: Kusunoki, M.