This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Galarneau, H. Articles by Vallières, L. Search for Related Content PubMed PubMed Citation Articles by Galarneau, H. Articles by Vallières, L.

Increased Glioma Growth in Mice Depleted of Macrophages

Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Quebec City, Quebec, Canada

Requests for reprints: Luc Vallières, Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, 2705 Laurier Boulevard, T3-67 Quebec City, Quebec, Canada G1V 4G2. Phone: 418-654-2296; Fax: 418-654-2761; E-mail: Luc.Vallieres{at}crchul.ulaval.ca.

Macrophages can promote the growth of some tumors, such as those of the breast and lung, but it is unknown whether this is true for all tumors, including those of the nervous system. On the contrary, we have previously shown that macrophages can slow the progression of malignant gliomas through a tumor necrosis factor–dependent mechanism. Here, we provide evidence suggesting that this antitumor effect could be mediated by T lymphocytes, as their number was drastically reduced in tumor necrosis factor–deficient mice and inversely correlated with glioma volume. However, this correlation was only observed in allogeneic recipients, prompting a reevaluation of the role of macrophages in a nonimmunogenic context. Using syngeneic mice expressing the herpes simplex virus thymidine kinase under the control of the CD11b promoter, we show that macrophages can exert an antitumor effect without the help of T lymphocytes. Macrophage depletion achieved by ganciclovir treatment resulted in a 33% increase in glioma volume. The antitumor effect of macrophages was not likely due to a tumoricidal activity because phagocytosis or apoptosis of glioma cells, transduced ex vivo with a lentiviral vector expressing green fluorescent protein, was rarely observed. Their antitumor effect was also not due to a destructive action on the tumor vasculature because macrophage depletion resulted in a modest reduction in vascular density. Therefore, this study suggests that macrophages can attenuate glioma growth by an unconventional mechanism. This study also validates a new transgenic model to explore the role of macrophages in cancer. [Cancer Res 2007;67(18):8874–81]

This article has been cited by other articles:

				D. S. Markovic, K. Vinnakota, S. Chirasani, M. Synowitz, H. Raguet, K. Stock, M. Sliwa, S. Lehmann, R. Kalin, N. van Rooijen, et al. Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion PNAS, July 28, 2009; 106(30): 12530 - 12535. [Abstract] [Full Text] [PDF]

				G. Gowing, T. Philips, B. Van Wijmeersch, J.-N. Audet, M. Dewil, L. Van Den Bosch, A. D. Billiau, W. Robberecht, and J.-P. Julien Ablation of Proliferating Microglia Does Not Affect Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase J. Neurosci., October 8, 2008; 28(41): 10234 - 10244. [Abstract] [Full Text] [PDF]