期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 30, 页码 12425-12430出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1106645108
关键词
chemoresistance; tumor progression
资金
- Uehara Memorial Research Awards
- Takeda Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Sagawa Foundation for Promotion of Cancer Research
- Institute for Genetic Medicine, Hokkaido University
- Grants-in-Aid for Scientific Research [21689031, 22240089, 23130501, 23591132, 23590534, 21249069] Funding Source: KAKEN
Recent evidence has unveiled the critical role of tumor cells with stem cell activities in tumorigenicity and drug resistance, but how tumor microenvironments regulate cancer stem/initiating cells (CSCs) remains unknown. We clarified the role of tumor-associated macrophages (TAMs) and their downstream factor milk-fat globule-epidermal growth factor-VIII (MFG-E8) in the regulation of CSC activities. Bone marrow chimeric systems and adoptive cell transfers elucidated the importance of MFG-E8 from TAMs in conferring to CSCs with the ability to promote tumorigenicity and anticancer drug resistance. MFG-E8 mainly activates signal transducer and activator of transcription-3 (Stat3) and Sonic Hedgehog pathways in CSCs and further amplifies their anticancer drug resistance in cooperation with IL-6. Thus, the pharmacological targeting of key factors derived from tumor-associated inflammation provides a unique strategy to eradicate therapy-resistant tumors by manipulating CSC activities.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据