© 1998 by Oxford University Press
Journal of the National Cancer Institute, Vol. 90, No. 21, 1648-1653,
November 4, 1998
©Copyright 1998 Oxford University Press
REPORTS |
Macrophage Role in the Anti-Prostate Cancer Response to One Class of Antiangiogenic Agents
Affiliations of authors: I. B. J. K. Joseph (The Johns Hopkins Oncology Center), J. T. Isaacs (The Johns Hopkins Oncology Center, Department of Urology), The Johns Hopkins University School of Medicine, Baltimore, MD.
Correspondence to: John T. Isaacs, Ph.D., The Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, 422 N. Bond St., Baltimore, MD 21231.
Abstract
Background. Tumor-associated macrophages (TAMs) can
either promote angiogenesis (i.e., the formation of new blood
vessels) in tumors by secreting tumor necrosis factor-
(TNF-) or inhibit angiogenesis by producing
granulocyte-macrophage colony-stimulating factor (GM-CSF), which
in turn stimulates production of the antiangiogenic protein
plasminogen activator inhibitor type 2 (PAI-2). We tested, alone
or in combination, the anti-prostate cancer activity of agents
that perturb macrophage function. Methods: By use of
enzyme-linked immunosorbent assays, we measured the effects of
Linomide® (roquinimex), thalidomide, pentoxifylline, and
genistein on TNF- and GM-CSF production in vitro by
virally transformed RAW 264.7 mouse macrophages and on PAI-2
production in vitro by human macrophages. The antitumor
effects of these agents were tested in vivo on
transplanted Dunning R-3327 MAT-Lu rat prostate cancers; TAM
numbers and blood vessel densities in these cancers were
determined by use of immunocytochemistry. Results:
Linomide selectively inhibited mouse macrophage secretion of
TNF- but not of GM-CSF; however, thalidomide,
pentoxifylline, and genistein inhibited the production of both
cytokines. Linomide, but not thalidomide or pentoxifylline,
increased production of PAI-2 by human macrophages. When
administered to rats bearing MAT-Lu tumors, each of the tested
agents reduced TAM numbers (Linomide, by 46%; thalidomide,
by 94%; pentoxifylline, by 71%; and genistein, by
96%). However, all of the agents reduced tumor blood
vessel density and tumor growth, with Linomide being the most
effective (44% reduction in blood vessel density and
69% inhibition of tumor growth). None of the other agents
potentiated Linomide's antitumor effect. Conclusions: Linomide is unique among the antiangiogenic agents tested,
in that it inhibits the stimulatory effects of TAMs on tumor
angiogenesis without eliminating their antiangiogenic effects,
and may thus prove to be more effective against prostate cancer.
[J Natl Cancer Inst 1998;90:1648-53]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Solinas, G. Germano, A. Mantovani, and P. Allavena Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation J. Leukoc. Biol., November 1, 2009; 86(5): 1065 - 1073. [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]
|
|
|
|
 |
|
 E. Obermueller, S. Vosseler, N. E. Fusenig, and M. M. Mueller Cooperative Autocrine and Paracrine Functions of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor in the Progression of Skin Carcinoma Cells Cancer Res., November 1, 2004; 64(21): 7801 - 7812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. De Larco, B. R. K. Wuertz, and L. T. Furcht The Potential Role of Neutrophils in Promoting the Metastatic Phenotype of Tumors Releasing Interleukin-8 Clin. Cancer Res., August 1, 2004; 10(15): 4895 - 4900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Satoh, T. Saika, S. Ebara, N. Kusaka, T. L. Timme, G. Yang, J. Wang, V. Mouraviev, G. Cao, E. M. A. Fattah, et al. Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model Cancer Res., November 15, 2003; 63(22): 7853 - 7860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Herbeuval, C. Lambert, O. Sabido, M. Cottier, P. Fournel, M. Dy, and C. Genin Macrophages From Cancer Patients: Analysis of TRAIL, TRAIL Receptors, and Colon Tumor Cell Apoptosis J Natl Cancer Inst, April 16, 2003; 95(8): 611 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. A. Duyndam, M. C. G. W. Hilhorst, H. M. M. Schluper, H. M. W. Verheul, P. J. van Diest, G. Kraal, H. M. Pinedo, and E. Boven Vascular Endothelial Growth Factor-165 Overexpression Stimulates Angiogenesis and Induces Cyst Formation and Macrophage Infiltration in Human Ovarian Cancer Xenografts Am. J. Pathol., February 1, 2002; 160(2): 537 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Izawa and C. P.N. Dinney The role of angiogenesis in prostate and other urologic cancers: a review Can. Med. Assoc. J., March 1, 2001; 164(5): 662 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dabrowska, J. Golab, A. Giermasz, M. Marczak, and M. Jakobisiak Re: Macrophage Role in the Anti-Prostate Cancer Response to One Class of Antiangiogenic Agents J Natl Cancer Inst, May 5, 1999; 91(9): 804b - 805b. [Full Text] [PDF]
|
|