SEARCH:   Advanced

Blood, 15 October 2004, Vol. 104, No. 8, pp. 2224-2234. Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2004-03-1109. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1109v1 104/8/2224    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Murdoch, C. Articles by Lewis, C. E. Search for Related Content PubMed PubMed Citation Articles by Murdoch, C. Articles by Lewis, C. E. Related Collections Neoplasia Phagocytes Cell Adhesion and Motility Review Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEW ARTICLES Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues Craig Murdoch, Athina Giannoudis, and Claire E. Lewis From the Tumor Targeting Group, Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, United Kingdom. The mechanisms responsible for recruiting monocytes from the bloodstream into solid tumors are now well characterized. However, recent evidence has shown that these cells then differentiate into macrophages and accumulate in large numbers in avascular and necrotic areas where they are exposed to hypoxia. This parallels their tendency to congregate in ischemic areas of other diseased tissues such as atherosclerotic plaques and arthritic joints. In tumors, macrophages appear to undergo marked phenotypic changes when exposed to hypoxia and to switch on their expression of a number of mitogenic and proangiogenic cytokines and enzymes. This then promotes tumor growth, angiogenesis, and metastasis. Here, we compare the various mechanisms responsible for monocyte recruitment into tumors with those regulating the accumulation of macrophages in hypoxic/necrotic areas. Because the latter are best characterized in human tumors, we focus mainly on these but also discuss their relevance to macrophage migration in ischemic areas of other diseased tissues. Finally, we discuss the relevance of these mechanisms to the development of novel cancer therapies, both in providing targets to reduce the proangiogenic contribution made by hypoxic macrophages in tumors and in developing the use of macrophages to deliver therapeutic gene constructs to hypoxic areas of diseased tissues. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Guruvayoorappan Tumor Versus Tumor-Associated Macrophages: How Hot is the Link? Integr Cancer Ther, June 1, 2008; 7(2): 90 - 95. [Abstract] [PDF] J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF] F. Battaglia, S. Delfino, E. Merello, M. Puppo, R. Piva, L. Varesio, and M. C. Bosco Hypoxia transcriptionally induces macrophage-inflammatory protein-3{alpha}/CCL-20 in primary human mononuclear phagocytes through nuclear factor (NF)-{kappa}B J. Leukoc. Biol., March 1, 2008; 83(3): 648 - 662. [Abstract] [Full Text] [PDF] S. K. Biswas, A. Sica, and C. E. Lewis Plasticity of Macrophage Function during Tumor Progression: Regulation by Distinct Molecular Mechanisms J. Immunol., February 15, 2008; 180(4): 2011 - 2017. [Abstract] [Full Text] [PDF] C.-S. Chiang, F.-H. Chen, J.-H. Hong, P.-S. Jiang, H.-L. Huang, C.-C. Wang, and W. H. McBride Functional phenotype of macrophages depends on assay procedures Int. Immunol., February 1, 2008; 20(2): 215 - 222. [Abstract] [Full Text] [PDF] U. Tigges, E. G. Hyer, J. Scharf, and W. B. Stallcup FGF2-dependent neovascularization of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages Development, February 1, 2008; 135(3): 523 - 532. [Abstract] [Full Text] [PDF] A. Weigert, N. Tzieply, A. von Knethen, A. M. Johann, H. Schmidt, G. Geisslinger, and B. Brune Tumor Cell Apoptosis Polarizes Macrophages Role of Sphingosine-1-Phosphate Mol. Biol. Cell, October 1, 2007; 18(10): 3810 - 3819. [Abstract] [Full Text] [PDF] G. T. Lee, J. H. Hong, C. Kwak, J. Woo, V. Liu, C. Lee, and I. Y. Kim Effect of Dominant Negative Transforming Growth Factor-{beta} Receptor Type II on Cytotoxic Activity of RAW 264.7, a Murine Macrophage Cell Line Cancer Res., July 15, 2007; 67(14): 6717 - 6724. [Abstract] [Full Text] [PDF] D.-M. Kuang, Y. Wu, N. Chen, J. Cheng, S.-M. Zhuang, and L. Zheng Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes Blood, July 15, 2007; 110(2): 587 - 595. [Abstract] [Full Text] [PDF] N. Bourdel, S. Matsuzaki, J.-E. Bazin, J.-L. Pouly, G. Mage, and M. Canis Peritoneal tissue-oxygen tension during a carbon dioxide pneumoperitoneum in a mouse laparoscopic model with controlled respiratory support Hum. Reprod., April 1, 2007; 22(4): 1149 - 1155. [Abstract] [Full Text] [PDF] C.-H. Cho, Y. Jun Koh, J. Han, H.-K. Sung, H. Jong Lee, T. Morisada, R. A. Schwendener, R. A. Brekken, G. Kang, Y. Oike, et al. Angiogenic Role of LYVE-1-Positive Macrophages in Adipose Tissue Circ. Res., March 2, 2007; 100(4): e47 - e57. [Abstract] [Full Text] [PDF] M. Puppo, M. C. Bosco, M. Federico, S. Pastorino, and L. Varesio Hypoxia inhibits Moloney murine leukemia virus expression in activated macrophages J. Leukoc. Biol., February 1, 2007; 81(2): 528 - 538. [Abstract] [Full Text] [PDF] A. E. M. Dirkx, M. G. A. oude Egbrink, J. Wagstaff, and A. W. Griffioen Monocyte/macrophage infiltration in tumors: modulators of angiogenesis J. Leukoc. Biol., December 1, 2006; 80(6): 1183 - 1196. [Abstract] [Full Text] [PDF] E. Y. Lin, J.-F. Li, L. Gnatovskiy, Y. Deng, L. Zhu, D. A. Grzesik, H. Qian, X.-n. Xue, and J. W. Pollard Macrophages Regulate the Angiogenic Switch in a Mouse Model of Breast Cancer Cancer Res., December 1, 2006; 66(23): 11238 - 11246. [Abstract] [Full Text] [PDF] K. Yamaji-Kegan, Q. Su, D. J. Angelini, H. C. Champion, and R. A. Johns Hypoxia-induced mitogenic factor has proangiogenic and proinflammatory effects in the lung via VEGF and VEGF receptor-2 Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1159 - L1168. [Abstract] [Full Text] [PDF] C. Lamagna, M. Aurrand-Lions, and B. A. Imhof Dual role of macrophages in tumor growth and angiogenesis J. Leukoc. Biol., October 1, 2006; 80(4): 705 - 713. [Abstract] [Full Text] [PDF] W.-Y. Chen, B.-C. Cheng, M.-J. Jiang, M.-Y. Hsieh, and M.-S. Chang IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2090 - 2095. [Abstract] [Full Text] [PDF] G. Melillo Inhibiting Hypoxia-Inducible Factor 1 for Cancer Therapy Mol. Cancer Res., September 1, 2006; 4(9): 601 - 605. [Abstract] [Full Text] [PDF] M. C. Bosco, M. Puppo, C. Santangelo, L. Anfosso, U. Pfeffer, P. Fardin, F. Battaglia, and L. Varesio Hypoxia Modifies the Transcriptome of Primary Human Monocytes: Modulation of Novel Immune-Related Genes and Identification Of CC-Chemokine Ligand 20 as a New Hypoxia-Inducible Gene J. Immunol., August 1, 2006; 177(3): 1941 - 1955. [Abstract] [Full Text] [PDF] B. Li, E. E. Sharpe, A. B. Maupin, A. A. Teleron, A. L. Pyle, P. Carmeliet, and P. P. Young VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization FASEB J, July 1, 2006; 20(9): 1495 - 1497. [Abstract] [Full Text] [PDF] M. A. Rahat, B. Marom, H. Bitterman, L. Weiss-Cerem, A. Kinarty, and N. Lahat Hypoxia reduces the output of matrix metalloproteinase-9 (MMP-9) in monocytes by inhibiting its secretion and elevating membranal association J. Leukoc. Biol., April 1, 2006; 79(4): 706 - 718. [Abstract] [Full Text] [PDF] J. Vakkila, R. Jaffe, M. Michelow, and M. T. Lotze Pediatric cancers are infiltrated predominantly by macrophages and contain a paucity of dendritic cells: a major nosologic difference with adult tumors. Clin. Cancer Res., April 1, 2006; 12(7): 2049 - 2054. [Abstract] [Full Text] [PDF] M. G. Frid, J. A. Brunetti, D. L. Burke, T. C. Carpenter, N. J. Davie, J. T. Reeves, M. T. Roedersheimer, N. van Rooijen, and K. R. Stenmark Hypoxia-Induced Pulmonary Vascular Remodeling Requires Recruitment of Circulating Mesenchymal Precursors of a Monocyte/Macrophage Lineage Am. J. Pathol., February 1, 2006; 168(2): 659 - 669. [Abstract] [Full Text] [PDF] C. E. Lewis and J. W. Pollard Distinct Role of Macrophages in Different Tumor Microenvironments Cancer Res., January 15, 2006; 66(2): 605 - 612. [Abstract] [Full Text] [PDF] C. Murdoch, M. Muthana, and C. E. Lewis Hypoxia Regulates Macrophage Functions in Inflammation J. Immunol., November 15, 2005; 175(10): 6257 - 6263. [Abstract] [Full Text] [PDF] C. Lewis and C. Murdoch Macrophage Responses to Hypoxia: Implications for Tumor Progression and Anti-Cancer Therapies Am. J. Pathol., September 1, 2005; 167(3): 627 - 635. [Abstract] [Full Text] [PDF] R. Cancello, C. Henegar, N. Viguerie, S. Taleb, C. Poitou, C. Rouault, M. Coupaye, V. Pelloux, D. Hugol, J.-L. Bouillot, et al. Reduction of Macrophage Infiltration and Chemoattractant Gene Expression Changes in White Adipose Tissue of Morbidly Obese Subjects After Surgery-Induced Weight Loss Diabetes, August 1, 2005; 54(8): 2277 - 2286. [Abstract] [Full Text] [PDF] C. Lamagna, K. M. Hodivala-Dilke, B. A. Imhof, and M. Aurrand-Lions Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth Cancer Res., July 1, 2005; 65(13): 5703 - 5710. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020