Experimental metastasis is suppressed in MMP-9-deficient mice

被引:278
作者
Itoh, T
Tanioka, M
Matsuda, H
Nishimoto, H
Yoshioka, T
Suzuki, R
Uehira, M
机构
[1] Shionogi & Co Ltd, Shionogi Inst Med Sci, Fukushima Ku, Osaka 5530002, Japan
[2] Shionogi & Co Ltd, Discovery Res Labs, Fukushima Ku, Osaka 5530002, Japan
关键词
experimental tumor metastasis; gelatinase; knockout mice; matrix metalloproteinase;
D O I
10.1023/A:1006603723759
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Matrix metalloproteinases (MMPs) are thought to play a key role in tumor invasion and metastasis. The role of MMP-9 (gelatinase B) in tumor metastasis was examined in MMP-9-deficient mice produced by gene targeting using embryonic stem cells. MMP-9-deficient mice develop normally and are fertile. In these mice, the number of metastatic colonies of B16-BL6 melanoma cells or Lewis lung carcinoma cells that were implanted intravenously fell by 45% for B16-BL6 melanoma and 59% for Lewis lung carcinoma (p=0.03 and p=0.0043, respectively). Gelatin zymography showed that both tumor cell lines did not secrete MMP-9 by themselves but the host cells surrounding the tumor cells secrete MMP-9 in vivo. These results indicated that host-derived MMP-9 plays an important role in the process of tumor metastasis.
引用
收藏
页码:177 / 181
页数:5
相关论文
共 21 条
[1]   SEQUENCE OF HUMAN-TISSUE INHIBITOR OF METALLOPROTEINASES AND ITS IDENTITY TO ERYTHROID-POTENTIATING ACTIVITY [J].
DOCHERTY, AJP ;
LYONS, A ;
SMITH, BJ ;
WRIGHT, EM ;
STEPHENS, PE ;
HARRIS, TJR ;
MURPHY, G ;
REYNOLDS, JJ .
NATURE, 1985, 318 (6041) :66-69
[2]   MICE DEVOID OF THE GLIAL FIBRILLARY ACIDIC PROTEIN DEVELOP NORMALLY AND ARE SUSCEPTIBLE TO SCRAPIE PRIONS [J].
GOMI, H ;
YOKOYAMA, T ;
FUJIMOTO, K ;
IKEDA, T ;
KATOH, A ;
ITOH, T ;
ITOHARA, S .
NEURON, 1995, 14 (01) :29-41
[3]  
HART IR, 1979, AM J PATHOL, V97, P587
[4]  
HIMELSTEIN BP, 1994, J CELL SCI, V107, P477
[5]  
HIMELSTEIN BP, 1994, INVAS METAST, V14, P246
[6]   Unaltered secretion of beta-amyloid precursor protein in gelatinase a (matrix metalloproteinase 2)-deficient mice [J].
Itoh, T ;
Ikeda, T ;
Gomi, H ;
Nakao, S ;
Suzuki, T ;
Itohara, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (36) :22389-22392
[7]  
Itoh T, 1998, CANCER RES, V58, P1048
[8]   METASTATIC POTENTIAL CORRELATES WITH ENZYMATIC DEGRADATION OF BASEMENT-MEMBRANE COLLAGEN [J].
LIOTTA, LA ;
TRYGGVASON, K ;
GARBISA, S ;
HART, I ;
FOLTZ, CM ;
SHAFIE, S .
NATURE, 1980, 284 (5751) :67-68
[9]   METALLOPROTEINASES AND THEIR INHIBITORS IN MATRIX REMODELING [J].
MATRISIAN, LM .
TRENDS IN GENETICS, 1990, 6 (04) :121-125
[10]  
Nielsen BS, 1996, INT J CANCER, V65, P57, DOI 10.1002/(SICI)1097-0215(19960103)65:1<57::AID-IJC10>3.0.CO