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Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells
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Journal Article
Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells
2011
Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Antigens, Surface - genetics
/ Antigens, Surface - immunology
/ Cancer
/ Cells
/ Hedgehog Proteins - immunology
/ Humans
/ Mice
/ milk fat
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - immunology
/ Neoplastic Stem Cells - pathology
/ RNA, Small Interfering - genetics
/ Signal Transduction - immunology
/ STAT3 Transcription Factor - antagonists & inhibitors
/ STAT3 Transcription Factor - genetics
/ STAT3 Transcription Factor - immunology
/ Tumor Microenvironment - immunology
/ Tumors
