Tumor-associated Macrophages Regulate Tumorigenicity and Anticancer Drug Responses of Cancer Stem/initiating Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Jul 13

PMID 21746895

Citations 273

Authors

Masahisa Jinushi

Shigeki Chiba

Hironori Yoshiyama

Kenkichi Masutomi

Ichiro Kinoshita

Hirotoshi Dosaka-Akita

Hideo Yagita

Akinori Takaoka

Hideaki Tahara

Affiliations

Soon will be listed here.

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.

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