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Title: Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth

Abstract

Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injectingmore » them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo.« less

Authors:
 [1];  [2];  [1];  [2];  [1];  [3];  [4];  [1];  [2];  [5];  [6];  [3];  [7]
  1. Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taiwan (China)
  2. (China)
  3. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan (China)
  4. Department of Pathology, Chang Gung University, Taiwan (China)
  5. Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan (China)
  6. Department of Radiation Oncology, Roy E. Coats Laboratories, University of California Los Angeles, Los Angeles, CA (United States)
  7. Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taiwan (China) and Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan (China). E-mail: jihong@adm.cgmh.org.tw
Publication Date:
OSTI Identifier:
20951671
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2007.01.041; PII: S0360-3016(07)00232-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ARGINASE; FRACTIONATED IRRADIATION; GROWTH; IN VIVO; MACROPHAGES; MICE; NEOPLASMS; NITRIC OXIDE; PROSTATE; RADIATION DOSES; TAMOXIFEN

Citation Formats

Tsai, C.-S., Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan, Chen, F.-H., Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan, Wang, C.-C., Huang, H.-L., Jung, Shih-Ming, Wu, C.-J., Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan, Lee, C.-C., McBride, William H., Chiang, C.-S., and Hong, J.-H.. Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2007.01.041.
Tsai, C.-S., Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan, Chen, F.-H., Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan, Wang, C.-C., Huang, H.-L., Jung, Shih-Ming, Wu, C.-J., Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan, Lee, C.-C., McBride, William H., Chiang, C.-S., & Hong, J.-H.. Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth. United States. doi:10.1016/j.ijrobp.2007.01.041.
Tsai, C.-S., Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan, Chen, F.-H., Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan, Wang, C.-C., Huang, H.-L., Jung, Shih-Ming, Wu, C.-J., Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan, Lee, C.-C., McBride, William H., Chiang, C.-S., and Hong, J.-H.. Fri . "Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth". United States. doi:10.1016/j.ijrobp.2007.01.041.
@article{osti_20951671,
title = {Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth},
author = {Tsai, C.-S. and Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan and Chen, F.-H. and Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan and Wang, C.-C. and Huang, H.-L. and Jung, Shih-Ming and Wu, C.-J. and Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan and Lee, C.-C. and McBride, William H. and Chiang, C.-S. and Hong, J.-H.},
abstractNote = {Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injecting them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo.},
doi = {10.1016/j.ijrobp.2007.01.041},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}