Crosstalk to Stromal Fibroblasts Induces Resistance of Lung Cancer to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
基质成纤维细胞的串扰诱导肺癌对表皮生长因子受体酪氨酸激酶抑制剂的耐药性
基本信息
- 批准号:21790768
- 负责人:
- 金额:$ 2.75万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Young Scientists (B)
- 财政年份:2009
- 资助国家:日本
- 起止时间:2009 至 2010
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Purpose : Lung cancers with EGFR activating mutations show good clinical response to gefitinib and erlotinib, selective TKIs to epidermal growth factor receptor (EGFR), but these tumors invariably develop drug resistance. Host stromal cells have been found to have a considerable effect on the behavior of cancer cells. Little is known, however, about the role of host cells on the sensitivity of cancer cells to receptor tyrosine kinase inhibitors (TKIs). We have therefore assessed the effect of crosstalk between stromal cells and lung cancer cells harboring EGFR mutations on susceptibility to EGFR-TKIs.Experimental design : We evaluated the gefitinib sensitivity of lung cancer cells with EGFR activating muations, PC-9 and HCC827, when co-cultured with fibroblasts and co-injected into SCID mice. We also examined the effect of lung cancer cells to fibroblasts recruitment.Results : Both human fibroblast cell lines and primary cultured fibroblasts produced various level of HGF. Lung cancer cells markedly recruited fibroblasts. The lung cancer cells became resistant to EGFR-TKIs when co-cultured in vitro with HGF-producing fibroblasts and co-injected into SCID mice. Importantly, combined use of gefitinib plus anti-HGF antibody or the HGF antagonist, NK4 successfully overcame the fibroblast-induced EGFR-TKI resistance both in vitro and in vivo. Co-localization of fibroblasts and HGF was detected in both xenograft tumors in mouse model and lung cancer patient specimens.Conclusions : These findings indicate that crosstalk to stromal fibroblasts plays a critical role in lung cancer resistance to EGFR-TKIs and may be an ideal therapeutic target in lung cancer with EGFR activating mutations.
目的:表皮生长因子受体(EGFR)基因突变的肺癌对吉非替尼和厄洛替尼有良好的临床疗效,对表皮生长因子受体(EGFR)有选择性的TKI治疗,但这些肿瘤往往会产生耐药性。宿主基质细胞被发现对癌细胞的行为有相当大的影响。然而,宿主细胞在癌细胞对受体酪氨酸激酶抑制剂(TKIs)敏感性上的作用知之甚少。因此,我们评估了基质细胞和携带EGFR突变的肺癌细胞之间的串扰对EGFR-TKIs易感性的影响。实验设计:我们评估了具有EGFR激活突变的肺癌细胞PC-9和HCC827与成纤维细胞共培养并共同注射到SCID小鼠中时吉非替尼的敏感性。结果:人成纤维细胞系和原代培养的成纤维细胞均能产生不同水平的HGF。肺癌细胞明显募集成纤维细胞。当肺癌细胞与产生HGF的成纤维细胞在体外共培养并共同注射到SCID小鼠中时,肺癌细胞对EGFR-TKIs产生了抗药性。重要的是,联合使用吉非替尼和抗HGF抗体或HGF拮抗剂,NK4在体内外都成功地克服了成纤维细胞诱导的EGFR-TKI耐药。在小鼠移植瘤模型和肺癌患者标本中均检测到成纤维细胞和HGF的共存。结论:间质成纤维细胞的串扰在肺癌对EGFR-TKI耐药中起关键作用,可能成为EGFR激活突变肺癌的理想治疗靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hepatocyte Growth Factor Reduces Susceptibility to an Irreversible Epidermal Growth Factor Receptor Inhibitor in EGFR-T790M Mutant Lung Cancer
- DOI:10.1158/1078-0432.ccr-09-1204
- 发表时间:2010-01-01
- 期刊:
- 影响因子:11.5
- 作者:Yamada, Tadaaki;Matsumoto, Kunio;Yano, Seiji
- 通讯作者:Yano, Seiji
E7080, a Multi-Tyrosine Kinase Inhibitor, Suppresses the Progression of Malignant Pleural Mesothelioma with Different Proangiogenic Cytokine Production Profiles
- DOI:10.1158/1078-0432.ccr-09-1980
- 发表时间:2009-12-01
- 期刊:
- 影响因子:11.5
- 作者:Ikuta, Kenji;Yano, Seiji;Sone, Saburo
- 通讯作者:Sone, Saburo
HM1.24 (CD317) is a novel target against lung cancer for immunothera py using anti-D41.24 antibody.
HM1.24 (CD317) 是使用抗 D41.24 抗体进行免疫治疗的肺癌新靶点。
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Wang W;et al.
- 通讯作者:et al.
Stromal fibroblasts induce resistance of lung cancer to EGFR tyrosine kinase inhibitors.13^<th> Japanese Association for Molecular Target Therapy of Cancer.
基质成纤维细胞诱导肺癌对EGFR酪氨酸激酶抑制剂的耐药性。13日本癌症分子靶向治疗协会。
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Wei Wang;Qi Li;Tadaaki Yamada;Yasuhiko Nishioka;Saburo Sone;Seiji Yano.
- 通讯作者:Seiji Yano.
Therapeutic effect of HGF inhibitors against HGF-induced EGFR-TKI resistance in lung cancer harboring EGFR mutations.
HGF 抑制剂对 HGF 诱导的 EGFR 突变肺癌的 EGFR-TKI 耐药的治疗效果。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Tanaka T;Fujita T;Nangaku M;矢野聖二
- 通讯作者:矢野聖二
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WANG Wei其他文献
Profiling of Gene Expression in the Reproductive Organs of Jatropha curcas
麻风树生殖器官基因表达谱分析
- DOI:
- 发表时间:
2011-06 - 期刊:
- 影响因子:0
- 作者:
WEI Bryan;WANG Lei;WANG Wei;PUN Sing;ZHANG Shi-hua;QING Dong-jin;LI Ning;WONG Wai-shing - 通讯作者:
WONG Wai-shing
GeoEye-1立体像对定位精度及其应用分析
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
王薇;赵利平;WANG Wei;ZHAO Li-ping - 通讯作者:
ZHAO Li-ping
Fabrication of a biomimetic controllable adhesive surface by ultraprecision multistep and layered scribing and casting molding
超精密多步分层划片浇铸成型仿生可控粘合表面
- DOI:
10.1007/s11431-020-1801-9 - 发表时间:
2021-06 - 期刊:
- 影响因子:4.6
- 作者:
WANG Wei;XIE ZongWu - 通讯作者:
XIE ZongWu
频率漂移不敏感太赫兹波透射测量系统设计
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
马无锡;HONG Zhi;刘建军;汪伟;李璟;洪治;MA Wu-xi;LIU Jian-jun;WANG Wei;LI Jing - 通讯作者:
LI Jing
A Linear Ce-III Complex Based on in-situ Generated N-hydroxy-1,8-naphthalenedicarboximide
- DOI:
10.14102/j.cnki.0254–5861.2011–3190 - 发表时间:
2021 - 期刊:
- 影响因子:
- 作者:
LIU Yang;CAO Xue-Li;WANG Wei;LI Guo-Ling;LI Shun;HUANG You-Gui - 通讯作者:
HUANG You-Gui
WANG Wei的其他文献
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{{ truncateString('WANG Wei', 18)}}的其他基金
The Research on Human Robot Interface Enabled with High Bandwidth Force Servoing for Manipulation of Robotic Arm
高带宽力伺服机械臂人机界面研究
- 批准号:
15K18009 - 财政年份:2015
- 资助金额:
$ 2.75万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
A study on the Factors Contributing to the cultural attraction of tourist resort with the Perspective of Iroke Ajike and Hitoke.
旅游胜地文化吸引力影响因素研究——伊罗克·阿吉克和希托克视角
- 批准号:
25570007 - 财政年份:2013
- 资助金额:
$ 2.75万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Transnational Migration and Culture : A Comparative Study on the Dissemination and Changes of Traditional Chinese Music and Performing Arts among Chinese Overseas
跨国移民与文化:中国传统音乐与表演艺术在海外华人传播与变迁的比较研究
- 批准号:
20520711 - 财政年份:2008
- 资助金额:
$ 2.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Comparative Studies on Changes in Chinese Society and Traditional Culture and Networks among Overseas Chinese Communities
中国社会变迁与海外华人传统文化与网络的比较研究
- 批准号:
17520557 - 财政年份:2005
- 资助金额:
$ 2.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Comparative Research on The Transmission and Reorganization of Traditional Culture Especially Festivals and Performances Among Overseas Chinese
华侨传统文化尤其节庆表演的传承与重组比较研究
- 批准号:
15520521 - 财政年份:2003
- 资助金额:
$ 2.75万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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