Journal
CELL CYCLE
Volume 9, Issue 24, Pages 4824-4835Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.24.14322
Keywords
interleukin-4; tumor-associated macrophage; tumor microenvironment; cytokines; cathepsin proteases
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Funding
- National Cancer Institute
- Breast Cancer Research Foundation
- Geoffrey Beene Foundation
- Frank L. Horsfall Jr. Fellowship
- Taiwan Merit Scholarship
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Although macrophages were originally recognized as major immune effector cells, it is now appreciated that they also play many important roles in the maintenance of tissue homeostasis, and are involved in a variety of pathological conditions including cancer. Several studies have demonstrated the contributions of tumor-associated macrophages (TAMs) to tumor initiation, progression and metastasis. However, the detailed mechanisms underlying how TAMs differ molecularly from their normal counterparts and how the conversion to TAMs occurs have only just begun to be understood. TAMs have been proposed to exhibit phenotypes of 'alternatively activated' macrophages, though there has been limited evidence directly linking the phenotypes of TAMs to the alternative activation of macrophages. This review will focus on IL-4, the prototypic cytokine that induces the alternative activation of macrophages, and review current knowledge regarding the contributions of IL-4 to the phenotypes of TAMs and its effects on tumorigenesis.
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