Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth.
Int J Radiat Oncol Biol Phys
; 68(2): 499-507, 2007 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-17398016
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 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginase
/
Neoplasias da Próstata
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Ciclo-Oxigenase 2
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Óxido Nítrico Sintase Tipo II
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Macrófagos
/
Proteínas de Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Int J Radiat Oncol Biol Phys
Ano de publicação:
2007
Tipo de documento:
Article