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Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells.


ABSTRACT: 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.

SUBMITTER: Jinushi M 

PROVIDER: S-EPMC3145680 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells.

Jinushi Masahisa M   Chiba Shigeki S   Yoshiyama Hironori H   Masutomi Kenkichi K   Kinoshita Ichiro I   Dosaka-Akita Hirotoshi H   Yagita Hideo H   Takaoka Akinori A   Tahara Hideaki H  

Proceedings of the National Academy of Sciences of the United States of America 20110711 30


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  ...[more]

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