Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs

被引:33
作者
Gauthier, N
Lohm, S
Touzery, C
Chantôme, A
Perette, B
Reveneau, S
Brunotte, F
Juillerat-Jeanneret, L
Jeannin, JF [1 ]
机构
[1] Univ Bourgogne, EPHE INSERM, Lab Immunol & Immunotherapie Canc, Unite 517, Dijon, France
[2] Univ Bourgogne, IFR 100, Dijon, France
[3] CHUV, Inst Univ Pathol, Lausanne, Switzerland
[4] Ctr Georges Francois Leclerc, Serv Med Nucl, Dijon, France
[5] INSERM, IFR 100, Dijon, France
关键词
D O I
10.1093/carcin/bgh158
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1beta increased NO production in both clones, and TNF-alpha had a synergistic effect on IL-1beta-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clones similarly located in the lungs of syngeneic mice 48 h after injection. However, EMT-6H cells were significantly more tumorigenic than EMT-6 J cells as assessed at later time points. Injection of EMT-6 J cells and simultaneous treatment of mice with aminoguanidine (AG), a NOS II inhibitor, significantly increased tumour formation. Injection of EMT-6H and EMT-6 J cells into NOS II-deficient mice resulted in a significant survival increase as compared with wild-type animals. Simultaneous administration of AG increased the death rate of NOS II-deficient mice injected with EMT-6 J cells. These results demonstrate that: (i) NO does not influence the early stages of tumour metastasis to the lungs and (ii) NOS II expression in tumour cells reduces, while NOS II expression in host cells enhances, tumour nodule development. In conclusion, the cellular origin and the local NO production are critical in the metastatic process.
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页码:1559 / 1565
页数:7
相关论文
共 44 条
[1]  
Botti C, 1997, EUR J NUCL MED, V24, P497
[2]  
DuenasGonzalez A, 1997, MODERN PATHOL, V10, P645
[3]   ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS [J].
GREEN, LC ;
WAGNER, DA ;
GLOGOWSKI, J ;
SKIPPER, PL ;
WISHNOK, JS ;
TANNENBAUM, SR .
ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) :131-138
[4]  
Gries A, 1998, CIRCULATION, V97, P1481
[5]   AMINOGUANIDINE SELECTIVELY INHIBITS INDUCIBLE NITRIC-OXIDE SYNTHASE [J].
GRIFFITHS, MJD ;
MESSENT, M ;
MACALLISTER, RJ ;
EVANS, TW .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 110 (03) :963-968
[6]   Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells [J].
Hirai, Y ;
Migita, K ;
Honda, S ;
Ueki, Y ;
Yamasaki, S ;
Urayama, S ;
Kamachi, M ;
Kawakami, A ;
Ida, H ;
Kita, M ;
Fukuda, T ;
Shibatomi, K ;
Kawabe, Y ;
Aoyagi, T ;
Eguchi, K .
LIFE SCIENCES, 2001, 68 (08) :913-920
[7]   Nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester inhibits tumor-induced angiogenesis in mammary tumors [J].
Jadeski, LC ;
Lala, PK .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1381-1390
[8]  
Jadeski LC, 2000, INT J CANCER, V86, P30, DOI 10.1002/(SICI)1097-0215(20000401)86:1<30::AID-IJC5>3.0.CO
[9]  
2-I
[10]   Nitric oxide-mediated promotion of mammary tumour cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinase [J].
Jadeski, LC ;
Chakraborty, C ;
Lala, PK .
INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (04) :496-504