Macrophages are important mediators of either tumor- or inflammation-induced lymphangiogenesis

• Published in: Cellular and molecular life sciences : CMLS Vol. 69; no. 6; pp. 897 - 914
• Main Author: Ji, Rui-Cheng
• Format: Journal Article
• Language: English
• Published: Basel SP Birkhäuser Verlag Basel 01-03-2012; Springer Nature B.V
• Subjects: Angiogenesis; Animals; Antigens, CD - physiology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell Adhesion Molecules - physiology; Cell Adhesion Molecules, Neuronal - physiology; Cell Biology; Cells; Humans; Immune response; Inflammation - physiopathology; Lectins, C-Type - physiology; Life Sciences; Lymphangiogenesis; Lymphocyte receptors; Macrophage Activation; Macrophages - physiology; Mannose Receptor; Mannose-Binding Lectins - physiology; Neoplasms - physiopathology; Receptors, Cell Surface - physiology; Receptors, CXCR4 - physiology; Receptors, Lymphocyte Homing - physiology; Review; Signal Transduction; Toll-Like Receptor 4 - physiology; Tumor Microenvironment; Tumors; Vascular Endothelial Growth Factor C - physiology; Vascular Endothelial Growth Factor Receptor-3 - physiology; Lymphatic endothelial cells; VEGFR-2/-3; Tumor; Inflammation; Macrophages; Lymphangiogenesis; VEGF-A/-C/-D
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-011-0848-6

The lymphatic system provides important functions for tissue fluid homeostasis and immune response. Lymphangiogenesis, the formation of new lymphatics, comprises a series of complex cellular events in vitro or in vivo, e.g., proliferation, differentiation, and sprouting. Recent evidence has implied that macrophages act as a direct structural contributor to lymphatic endothelial walls or secret VEGF-C/-D and VEGF-A to initiate lymphangiogenesis in inflamed or tumor tissues. Bone marrow-derived macrophages are versatile cells that express different functional programs in response to exposure to microenvironmental signals, and can be identified by specific expression of a number of proteins, F4/80, CD11b, and CD68. Several causative factors, e.g., NF-κB, IL-1β, TNF-α, SDF-1, M-CSF, especially TonEBP/VEGF-C signaling, may be actively involved in macrophage-induced lymphangiogenesis. Alteration of macrophage phenotype and function has a profound effect on the development and progression of inflammation and malignancy, and macrophage depletion for controlling lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic-associated diseases.