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[Cancer Research 66, 605-612, January 15, 2006]
© 2006 American Association for Cancer Research

Reviews

Distinct Role of Macrophages in Different Tumor Microenvironments

Claire E. Lewis1 and Jeffrey W. Pollard2

1 Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom and 2 Center for the Study of Reproductive Biology and Women's Health, Departments of Developmental and Molecular Biology and Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, New York

Requests for reprints: Claire E. Lewis, Academic Unit of Pathology, Division of Genomic Medicine, Floor E, The Henry Wellcome Laboratories for Medical Research, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom. Phone: 44-114-271-2903; Fax: 44-114-226-1464; E-mail: Claire.lewis{at}sheffield.ac.uk.

Macrophages are prominent in the stromal compartment of virtually all types of malignancy. These highly versatile cells respond to the presence of stimuli in different parts of tumors with the release of a distinct repertoire of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and/or metastasis. The distinct microenvironments where tumor-associated macrophages (TAM) act include areas of invasion where TAMs promote cancer cell motility, stromal and perivascular areas where TAMs promote metastasis, and avascular and perinecrotic areas where hypoxic TAMs stimulate angiogenesis. This review will discuss the evidence for differential regulation of TAMs in these microenvironments and provide an overview of current attempts to target or use TAMs for therapeutic purposes. (Cancer Res 2006; 66(2): 605-12)




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M. Subramanian and C. Shaha
Up-Regulation of Bcl-2 through ERK Phosphorylation Is Associated with Human Macrophage Survival in an Estrogen Microenvironment
J. Immunol., August 15, 2007; 179(4): 2330 - 2338.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
P. Sinha, V. K. Clements, S. K. Bunt, S. M. Albelda, and S. Ostrand-Rosenberg
Cross-Talk between Myeloid-Derived Suppressor Cells and Macrophages Subverts Tumor Immunity toward a Type 2 Response
J. Immunol., July 15, 2007; 179(2): 977 - 983.
[Abstract] [Full Text] [PDF]

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 BloodHome page
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]

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 BloodHome page
M. A. Venneri, M. D. Palma, M. Ponzoni, F. Pucci, C. Scielzo, E. Zonari, R. Mazzieri, C. Doglioni, and L. Naldini
Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
Blood, June 15, 2007; 109(12): 5276 - 5285.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
E. Y. Lin and J. W. Pollard
Tumor-Associated Macrophages Press the Angiogenic Switch in Breast Cancer
Cancer Res., June 1, 2007; 67(11): 5064 - 5066.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. Cheng, D.-H. Huo, D.-M. Kuang, J. Yang, L. Zheng, and S.-M. Zhuang
Human Macrophages Promote the Motility and Invasiveness of Osteopontin-Knockdown Tumor Cells
Cancer Res., June 1, 2007; 67(11): 5141 - 5147.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
C. Murdoch, S. Tazzyman, S. Webster, and C. E. Lewis
Expression of Tie-2 by Human Monocytes and Their Responses to Angiopoietin-2
J. Immunol., June 1, 2007; 178(11): 7405 - 7411.
[Abstract] [Full Text] [PDF]

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 JCOHome page
H. Schmidt, S. Suciu, C. J.A. Punt, M. Gore, W. Kruit, P. Patel, D. Lienard, H. von der Maase, A. M.M. Eggermont, and U. Keilholz
Pretreatment Levels of Peripheral Neutrophils and Leukocytes As Independent Predictors of Overall Survival in Patients With American Joint Committee on Cancer Stage IV Melanoma: Results of the EORTC 18951 Biochemotherapy Trial
J. Clin. Oncol., April 20, 2007; 25(12): 1562 - 1569.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
J. D.W. van der Bilt, M. E. Soeters, A. M.M.J. Duyverman, M. W. Nijkamp, P. O. Witteveen, P. J. van Diest, O. Kranenburg, and I. H.M. Borel Rinkes
Perinecrotic Hypoxia Contributes to Ischemia/Reperfusion-Accelerated Outgrowth of Colorectal Micrometastases
Am. J. Pathol., April 1, 2007; 170(4): 1379 - 1388.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
C. Armani, E. Catalani, A. Balbarini, P. Bagnoli, and D. Cervia
Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages
J. Leukoc. Biol., March 1, 2007; 81(3): 845 - 855.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. M. Park, Y. Kanaoka, N. Eguchi, K. Aritake, S. Grujic, A. M. Materi, V. S. Buslon, B. L. Tippin, A. M. Kwong, E. Salido, et al.
Hematopoietic Prostaglandin D Synthase Suppresses Intestinal Adenomas in ApcMin/+ Mice
Cancer Res., February 1, 2007; 67(3): 881 - 889.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
K. Zins, D. Abraham, M. Sioud, and S. Aharinejad
Colon Cancer Cell-Derived Tumor Necrosis Factor-{alpha} Mediates the Tumor Growth-Promoting Response in Macrophages by Up-regulating the Colony-Stimulating Factor-1 Pathway
Cancer Res., February 1, 2007; 67(3): 1038 - 1045.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
E. F. Redente, D. J. Orlicky, R. J. Bouchard, and A. M. Malkinson
Tumor Signaling to the Bone Marrow Changes the Phenotype of Monocytes and Pulmonary Macrophages during Urethane-Induced Primary Lung Tumorigenesis in A/J Mice
Am. J. Pathol., February 1, 2007; 170(2): 693 - 708.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb
Multiple Etiologies of Tumor Hypoxia Require Multifaceted Solutions
Clin. Cancer Res., January 15, 2007; 13(2): 375 - 377.
[Full Text] [PDF]

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 J. Leukoc. Biol.Home page
A. Budhu and X. W. Wang
The role of cytokines in hepatocellular carcinoma
J. Leukoc. Biol., December 1, 2006; 80(6): 1197 - 1213.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. L. Ramnaraine, W. E. Mathews, J. M. Donohue, C. M. Lynch, M. J. Goblirsch, and D. R. Clohisy
Osteoclasts Direct Bystander Killing of Bone Cancer.
Cancer Res., November 15, 2006; 66(22): 10929 - 10935.
[Abstract] [Full Text] [PDF]

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 J. Leukoc. Biol.Home page
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]

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 Molecular Cancer TherapeuticsHome page
J. Wang, L. He, C. A. Combs, G. Roderiquez, and M. A. Norcross
Dimerization of CXCR4 in living malignant cells: control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions.
Mol. Cancer Ther., October 1, 2006; 5(10): 2474 - 2483.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
Y. Maruyama, M. Ono, A. Kawahara, T. Yokoyama, Y. Basaki, M. Kage, S. Aoyagi, H. Kinoshita, and M. Kuwano
Tumor Growth Suppression in Pancreatic Cancer by a Putative Metastasis Suppressor Gene Cap43/NDRG1/Drg-1 through Modulation of Angiogenesis.
Cancer Res., June 15, 2006; 66(12): 6233 - 6242.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. P. Nunez, W.-J. Oh, J. Rozenberg, C. Perella, M. Anver, J. C. Barrett, S. N. Perkins, D. Berrigan, J. Moitra, L. Varticovski, et al.
Accelerated Tumor Formation in a Fatless Mouse with Type 2 Diabetes and Inflammation.
Cancer Res., May 15, 2006; 66(10): 5469 - 5476.
[Abstract] [Full Text] [PDF]

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 JEMHome page
N. Martin-Orozco and C. Dong
New battlefields for costimulation
J. Exp. Med., April 17, 2006; 203(4): 817 - 820.
[Abstract] [Full Text] [PDF]


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