Molecular mechanisms responsible for the development of scirrhous gastric cancer: analysis of cancer stem cells.

导致硬质胃癌发生的分子机制：癌症干细胞分析。

• 批准号: 22390262
• 负责人: HIRAKAWA Kosei
• 金额: $ 11.65万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390262/
• 关键词: スキルス胃癌; 癌幹細胞; 胃癌由来線維芽細胞; TGFβ; integrin; 腹膜転移; スキルス胃癌細胞; 癌由来線維芽細胞; がん幹細胞; 抗癌剤耐性能; 腹膜転移能; 抗癌剤耐性; Met阻害剤; 分子標的治療; 微小環境; 抗癌剤

Scirrrhous gastric cancer frequently develops into peritoneal metastasis, resulting in a poor prognosis. Cancer stem cells (CSCs) are considered to be responsible for cancer metastasis. The side population (SP), as evaluated by a flowcytometic analysis has been known as CSCs rich population. The aim of this study is to clarify the characterization of the SP cells in peritoneal metastasis of gastric carcinoma and to determine an effective signal inhibitor with effects on the proliferation of CSC. We used three gastric cancer cell lines and three SP-enriched CSC cell lines. CSCs-like SP cells expressing integrin, and CD44 may play an important role for peritoneal metastasis in gastric carcinoma. CSCs have chemoresistance to irinotecan. c-Met inhibitor may be a promising target molecule for irinotecan-based chemotherapy of gastric cancer. CAFs might regulate the stemness of CSCs in scirrhous gastric cancer by TGF-beta signaling.

硬质胃癌常发生腹膜转移，预后较差。癌症干细胞（CSC）被认为是导致癌症转移的原因。通过流式细胞分析评估的侧群 (SP) 被称为 CSC 丰富群。本研究的目的是阐明胃癌腹膜转移中SP细胞的特征，并确定一种有效的信号抑制剂，对CSC的增殖产生影响。我们使用了三种胃癌细胞系和三种富含 SP 的 CSC 细胞系。表达整合素和CD44的CSC样SP细胞可能在胃癌腹膜转移中发挥重要作用。 CSC 对伊立替康具有化学耐药性。 c-Met 抑制剂可能是基于伊立替康的胃癌化疗的一个有前景的靶分子。 CAF 可能通过 TGF-β 信号传导调节硬质胃癌中 CSC 的干性。

项目成果

A c-Met Inhibitor Increases the Chemosensitivity of Cancer Stem Cells to the Irinotecan Active Metabolite SN38 in Gastric Carcinoma

c-Met 抑制剂可提高胃癌干细胞对伊立替康活性代谢物 SN38 的化学敏感性

• 发表时间: 2013
• 作者: Masakazu Yashiro;Tatsunari Fukuoka;Haruhito Kinoshita;Takafumi Nishii;Tsuyoshi Hasegawa;Taro Matsuzaki;Tamami Morisaki;Naoshi Kubo;Hiroaki Tanaka;Kazuya Muguruma;Masaichi Ohira;Kosei Hirakawa
• 通讯作者: Kosei Hirakawa

Role of the Stemness Factors Sox2, Oct3/4, and Nanog in Gastric Carcinoma

• DOI: 10.1016/j.jss.2010.11.903
• 发表时间: 2012-05-01
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Matsuoka, Junko;Yashiro, Masakazu;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei

Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis

• DOI: 10.1016/j.jconrel.2012.01.038
• 发表时间: 2012-04-30
• 期刊: JOURNAL OF CONTROLLED RELEASE
• 影响因子: 10.8
• 作者: Rafi, Md;Cabral, H.;Kataoka, K.
• 通讯作者: Kataoka, K.

Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-β signaling

• DOI: 10.1002/ijc.28520
• 发表时间: 2014-04-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Hasegawa, Tsuyoshi;Yashiro, Masakazu;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei

Borrmann's Macroscopic Criteria and p-Smad2 Expression Are Useful Predictive Prognostic Markers for Cytology-Positive Gastric Cancer Patients Without Overt Peritoneal Metastasis

• DOI: 10.1245/s10434-011-1768-2
• 发表时间: 2011-12-01
• 期刊: ANNALS OF SURGICAL ONCOLOGY
• 影响因子: 3.7
• 作者: Noda, Satoru;Yashiro, Masakazu;Hirakawa, Kosei
• 通讯作者: Hirakawa, Kosei