Year: 2012
Type: article
Abstract: Epidemiological studies have highlighted associations between the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) and reduced cancer risks in humans.Most NSAIDs function as cyclooxygenase-2 (COX-2) inhibitors that prevent production of prostaglandin E 2 (PGE 2 ).PGE 2 induces myeloid-derived suppressor cells (MDSCs), and NSAIDs reduce vascular endothelial growth factor (VEGF)-D production to inhibit lymphatic vessel dilation and eventually cancer metastasis.Based on these findings, we hypothesized that an NSAID-based COX-2 blockade would suppress brain metastasis of cancers by inhibiting MDSC development and chemokinemediated accumulation in the tumor microenvironment (TME).Because lung cancer causes brain metastases most frequently, we decided to focus on this type of cancer.In a murine brain tumor model using a syngenic LL/2 lung cancer cell line, treatment with NSAIDs reduced systemic PGE 2 production levels and significantly inhibited the formation of brain tumors.Moreover, the treatment reduced the MDSC-attracting chemokine CCL2 in the TME.Flow cytometric analyses revealed decreases in monocytic and granulocytic MDSCs in the bone marrow as well as in the TME in response to the NSAID-based treatment.Taken together, our findings show that the COX-2 pathway promotes brain metastases of lung cancers by supporting systemic development of MDSCs and their accumulation in the TME mediated by the corresponding chemokines.
Source: Neuro-Oncology
Authors: M. Fujita, R. Zhang, S. Nakata, K. Kuzushima, D. A. Wainwright, I. V. Balyasnikova, B. Auffinger, A. U. Ahmed, Y. Han, M. S. Lesniak, A. Knight, H. Arnouk, G. Y. Gillespie, W. Britt, Y. Su, M. W. Lowdell, L. S. Lamb, J. Wang, L. Leiss, B. D. Choi, C.-T. Kuan, M. Cai, D. D. Bigner, J. H. Sampson, I. Shibahara, R. Saito, R. Zhang, M. Kanamori, Y. Sonoda, T. Kumabe, T. Kikuchi, T. So, N. Ishii, T. Tominaga, L. Zhang, H. Wang, I. Zhang, X. Chen, A. Da Fonseca, H. Fan, B. Badie, E. J. Sayour, P. McLendon, R. Reynolds, D. D. Bigner, J. H. Sampson, R. McLendon, D. A. Mitchell, E. J. Sayour, L. Sanchez-Perez, C. Pham, D. Snyder, W. Xie, X. Cui, D. D. Bigner, J. H. Sampson, D. A. Mitchell, M. J. McConnell, K. W. Broadley, K. Farrand, A. Authier, J. H. Brown, M. Hunn, I. Hermans, G. Cantini, F. Pisati, S. Pessina, G. Finocchiaro, S. Pellegatta, J. T. Yeung, R. Hamilton, I. Pollack, R. Jakacki, H. Okada, L. Sanchez-Perez, B. Choi, D. Snyder, X. Cui, R. J. Schmittling, C. Flores, L. Johnson, G. A. Archer, D. D. Bigner, D. A. Mitchell, J. H. Sampson, B. Raychaudhuri, P. Rayman, P. Huang, J. Ireland, S. Donnola, D. Hamburdzumyan, J. Finke, M. A. Vogelbaum, K. Batich, D. Snyder, W. Xie, E. Reap, G. Archer, J. Sampson, D. Mitchell, A. M. Martin, C. Nirschl, M. Polanczyk, K. J. Cohen, D. M. Pardoll, C. G. Drake, M. Lim, W. C. Rutledge, J. Kong, J. Gao, D. A. Gutman, L. A. Cooper, C. Chisolm, L. Scarpace, T. Mikkelsen, J. H. Saltz, C. S. Moreno, D. J. Brat, R. G. Everson, D. N. Lisiero, H. Soto, L. M. Liau, R. M. Prins, L. Zhang, G. C. Gonzalez, M. Chae, T. E. Peterson, I. F. Parney, M. Chae, T. E. Peterson, A. J. Johnson, I. F. Parney
Institutions: Kindai University, Aichi Cancer Center, University of Chicago
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2329937296