Treatment strategy of pancreatic cancer by regulating FGFR2IIIc isoform

调控FGFR2IIIc亚型的胰腺癌治疗策略

• 批准号: 22591531
• 负责人: ISHIWATA Toshiyuki
• 金额: $ 2.75万
• 依托单位: Nippon Medical School
• 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-22591531/
• 关键词: FGFR-2 IIIc; ESRP1; siRNA; 癌幹細胞; 選択的スプライシング; 線維芽細胞増殖; 因子受容体; 線維芽細胞増殖因子受容体; FGFR2IIIc; 細胞増殖因子受容体; FGFR2 IIIc; ESRP-1

Fibroblast Growth Factor Receptor 2 IIIc (FGFR-2 IIIc) was abundant in 70% of pancreatic cancer cases, which correlated with the decreased duration of the development of liver metastasis after surgery. FGFR-2 IIIc transfected cells exhibited increased proliferation in vitro and formed larger subcutaneous and orthotopic tumors. Suppression of FGFR-2 IIIc expression inhibited the proliferation of pancreatic cancer cells, whereas an anti-FGFR-2 IIIc antibody inhibited the proliferation and migration of the cells (Ishiwata et al., Am J Pathol, 2012). Epithelial Splicing Regulatory Protein1 (ESRP1) binds the FGFR2 in the intron between exon IIIb and IIIc, and primarily promotes FGFR-2 IIIb expression. ESRP1 transfected pancreatic cancer cells formed significantly fewer liver metastases as compared to control cells. Thus, high FGFR-2 IIIc levels in pancreatic cancer contribute to disease aggressiveness, and FGFR-2 IIIc may be a noveland important therapeutic target in pancreatic cancer.

在70％的胰腺癌病例中，成纤维细胞生长因子受体2 IIIC（FGFR-2 IIIC）丰富，这与手术后肝转移的持续时间降低有关。 FGFR-2 IIIC转染的细胞在体外表现出增加的增殖，并形成较大的皮下和原位肿瘤。 FGFR-2 IIIC表达的抑制抑制了胰腺癌细胞的增殖，而抗FGFR-2 IIIC抗体抑制了细胞的增殖和迁移（Ishiwata等，Am J Pathol，2012）。上皮剪接调节蛋白1（ESRP1）结合了外显子IIIB和IIIC之间内含子中的FGFR2，并主要促进FGFR-2 IIIB表达。与对照细胞相比，ESRP1转染的胰腺癌细胞形成的肝转移量明显少得多。因此，胰腺癌中的高FGFR-2 IIIC水平高导致疾病的侵略性，而FGFR-2 IIIC可能是胰腺癌中Noveland的重要治疗靶标。

项目成果

Fibroblast growth factor receptor 2 as a novel therepeutic target for pancreatic cancer

成纤维细胞生长因子受体2作为胰腺癌的新治疗靶点

• 发表时间: 2010
• 作者: Furukawa T;Hatori T;Fujita I;Yamamoto M;Kobayashi M;Ohike N;Morohoshi T;Egawa S;Unno M;Takao S;Osako M;Yonezawa S;Mino-Kenudson M;Lauwers GY;Yamaguchi H;Ban S;Shimizu M.;Ishiwata T
• 通讯作者: Ishiwata T

Secreted 70 kiloDalton lumican stimulates growthand inhibits invasion of human pancreatic cancer.

分泌的 70 kiloDalton lumican 刺激生长并抑制人类胰腺癌的侵袭。

• 发表时间: 2012
• 期刊: Cancer Letters
• 影响因子: 9.7
• 作者: Yamamoto T;Matsuda Y;Kawahara K;Ishiwata T;Naito Z
• 通讯作者: Naito Z

Clinicopathological Features of Thirty Autopsy Cases of Pancreatic Carcinoma

胰腺癌尸检30例临床病理特征

• 期刊: J Nippon Med Sch
• 影响因子: 1
• 作者: Matsuda Y;Hagio M;Naito Z;Ishiwata T
• 通讯作者: Ishiwata T

Nestin as a novel therapeutic target for pancreatic cancer via tumor angiogenesis

• DOI: 10.3892/ijo.2012.1333
• 发表时间: 2012-05-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Yamahatsu, Kazuya;Matsuda, Yoko;Naito, Zenya
• 通讯作者: Naito, Zenya

Nestin and other putative cancer stem cell markers in pancreatic cancer

• DOI: 10.1007/s00795-012-0571-x
• 发表时间: 2012-06-01
• 期刊: MEDICAL MOLECULAR MORPHOLOGY
• 影响因子: 1.8
• 作者: Matsuda, Yoko;Kure, Shoko;Ishiwata, Toshiyuki
• 通讯作者: Ishiwata, Toshiyuki