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.

我们假设直肠癌放化疗（CRT）后残留的癌细胞具有治疗（CRT）抗性，与CRT前的癌症标本相比，含有推定的CSC。此外，CRT存活的残余癌细胞可获得EMT诱导的转移潜能。CRT后残留癌细胞上CD 133、含亮氨酸重复序列的G蛋白偶联受体5（LGR 5）、葡萄糖转运蛋白1（GLUT 1）和缺氧诱导因子-1 α（HIF-1α）的表达与癌症复发和患者预后相关。胸苷酸合成酶（TS）和二氢嘧啶脱氢酶（DPD）在CRT后残留癌细胞上的表达也与癌症复发有关。CRT后CXCR 4及其配体CXCL 12、成纤维细胞活化蛋白-α（FAP-α）和基质细胞衍生因子-1（SDF-1）在癌间质上的表达也与癌症复发和患者预后相关。在体外研究中，辐射诱导大肠癌细胞发生EMT，从而获得侵袭和转移特性。神经营养受体原肌球蛋白相关激酶（TrkB）也诱导大肠癌细胞EMT。TrkB与E-cadherin呈负相关，与结直肠癌患者预后不良相关。CD 133以辐射剂量依赖性方式增加，尽管克隆性辐射存活细胞的数量减少。

项目成果

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

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

K. Tanaka, Y. Morimoto, Y. Toiyama, S. Saigusa, Y. Okugawa, Y. Inoue, K. Uchida, K. Matsushita, M. Kawamura, A. Mizoguchi, M. Kusunoki

K. Tanaka、Y. Morimoto、Y. Toiyama、S. Saigusa、Y. Okukawa、Y. Inoue、K. Uchida、K. Matsushita、M. Kawamura、A. Mizoguchi、M. Kusunoki

• 发表时间: 2012
• 作者: In vivo real-time imaging of tumor microcirculatory alterations in colorectal liver metastatic xenografts by chemotherapy using multiphoton microscopy.J Clin Oncol 30;2012 (suppl; abstr e21053);Intravital evaluation of time-course efficacy of anticancer drugs on colorectal liver metastases in the same living mice using two-photon laser scanning microscopy.J Clin Oncol 29: 2011 (suppl; abstr 10621)
• 通讯作者: Intravital evaluation of time-course efficacy of anticancer drugs on colorectal liver metastases in the same living mice using two-photon laser scanning microscopy.J Clin Oncol 29: 2011 (suppl; abstr 10621)

化学放射線療法後の遺残食道癌細胞における抗癌剤感受性遺伝子発現

放化疗后残留食管癌细胞抗癌药物敏感性基因的表达

• 发表时间: 2012
• 作者: Koji Tanaka;Masato Okigami;Yuhki Morimoto;Kohei Matsushita;Mikio Kawamura;Kiyoshi Hashimoto;Yuji Toiyama;Susumu Saigusa;Yoshinaga Okugawa;Yuhki Koike;Yasuhiro Inoue,Toshimitsu Araki;Keiichi Uchida;Yasuhiko Mohri;Akira Mizoguchi;Masato Kusuno;田中光司
• 通讯作者: 田中光司

Koji Tanaka, Yuhki Morimoto, Yuji Toiyama, Hiromi Yasuda, Susumu Saigusa, Takeshi Yokoe, Toshimitsu Araki, Yasuhiro Inoue, Chikao Miki, Masato Kusunoki.

田中浩二、森本雄纪、户山雄二、安田宏美、西草进、横江武、荒木敏光、井上泰宏、三木知功、楠木雅人。

• 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;cell transcription factors on colorectal carcinoma and adenoma in familial adenomatous polyposis (3358)
• 通讯作者: cell transcription factors on colorectal carcinoma and adenoma in familial adenomatous polyposis (3358)