Irradiation Promotes an M2 Macrophage Phenotype in Tumor Hypoxia
Open Access
- 1 January 2012
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Oncology
- Vol. 2, 1-12
- https://doi.org/10.3389/fonc.2012.00089
Abstract
Macrophages display different phenotypes with distinct functions and can rapidly respond to environmental changes. Previous studies on TRAMP-C1 tumor model have shown that irradiation has a strong impact on tumor microenvironments. The major changes include the decrease of microvascular density (MVD), the increase of avascular hypoxia, and the aggregation of tumor associated macrophages (TAMs) in avascular hypoxic regions. Similar changes were observed no matter the irradiation was given to tissue bed before tumor implantation (pre-IR tumors), or to established tumors (IR tumors). Recent results on three murine tumors, TRAMP-C1 prostate adenocarcinoma, ALTS1C1 astrocytoma, and GL261 glioma, further demonstrate that different phenotypes of inflammatory cells are spatially distributed into different microenvironments in both IR and pre-IR tumors. Regions with avascular hypoxia and central necrosis have CD11bhigh/Gr-1+ neutrophils in the center of the necrotic area. Next to them are CD11blow/F4/80+ macrophages that sit at the junctions between central necrotic and surrounding hypoxic regions. The majority of cells in the hypoxic regions are CD11blow/CD68+ macrophages. These inflammatory cell populations express different levels of Arg I. This distribution pattern, except for neutrophils, is not observed in tumors receiving chemotherapy or an anti-angiogenesis agent which also lead to avascular hypoxia. This unique distribution pattern of inflammatory cells in IR tumor sites is interfered with by targeting the expression of a chemokine protein, SDF-1, by tumor cells, and this also increases radiation-induced tumor growth delay. This indicates that irradiated-hypoxia tissues have distinct tumor microenvironments that favor the development of M2 macrophages and that is affected by the levels of tumor-secreted SDF-1.Keywords
This publication has 55 references indexed in Scilit:
- Vasculatures in Tumors Growing From Preirradiated Tissues: Formed by Vasculogenesis and Resistant to Radiation and Antiangiogenic TherapyInternational Journal of Radiation Oncology*Biology*Physics, 2011
- Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomasNanomedicine: Nanotechnology, Biology and Medicine, 2010
- Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitmentProceedings of the National Academy of Sciences of the United States of America, 2010
- pH-Responsive Polymeric siRNA Carriers Sensitize Multidrug Resistant Ovarian Cancer Cells to Doxorubicin via Knockdown of Polo-like Kinase 1Molecular Pharmaceutics, 2010
- Radiotherapy Decreases Vascular Density and Causes Hypoxia with Macrophage Aggregation in TRAMP-C1 Prostate TumorsClinical Cancer Research, 2009
- Matrix Metalloproteinase-9 Is Required for Tumor Vasculogenesis but Not for Angiogenesis: Role of Bone Marrow-Derived Myelomonocytic CellsCancer Cell, 2008
- Functional phenotype of macrophages depends on assay proceduresInternational Immunology, 2007
- Hypoxia-Induced Gene Expression in Human Macrophages: Implications for Ischemic Tissues and Hypoxia-Regulated Gene TherapyThe American Journal of Pathology, 2003
- The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapiesThe Journal of Pathology, 2002
- Expression of HIF‐1α by human macrophages: implications for the use of macrophages in hypoxia‐regulated cancer gene therapyThe Journal of Pathology, 2001