Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model

被引:178
作者
Mendes, O [1 ]
Kim, HT [1 ]
Stoica, G [1 ]
机构
[1] Texas A&M Univ, Coll Vet Med, Dept Pathobiol, College Stn, TX 77843 USA
关键词
animal model; brain metastasis; breast cancer; MMP2; MMP3; MMP9;
D O I
10.1007/s10585-005-8115-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In order to study the expression of MMP2, MMP3 and MMP9 in breast cancer brain metastasis, we used a syngeneic rat model of distant metastasis of ENU1564, a carcinogen-induced mammary adenocarcinoma cell line. At six weeks post inoculation we observed development of micro-metastasis in the brain. Immunohistochemistry and Western Blotting analyses showed that MMP-2, -3 and -9 proteins expressions are consistently significantly higher in neoplastic brain tissue compared to normal brain tissue. These results were confirmed by RT-PCR. In situ zymography revealed gelatinase activity within the brain metastasis. Gel zymography showed increase in MMP2 and MMP3 activity in brain metastasis. Furthermore, we were able to significantly decrease the development of breast cancer brain metastasis in animals by treatment with PD 166793, a selective synthetic MMP inhibitor. In addition, PD 166793 decreased the in vitro invasive cell behavior of ENU1546. Together our results suggest that MMP-2, -3 and -9 may be involved in the process of metastasis of breast cancer to the brain.
引用
收藏
页码:237 / 246
页数:10
相关论文
共 49 条
  • [1] Essential role for ERK mitogen-activated protein kinase in matrix metalloproteinase-9 regulation in rat cortical astrocytes
    Arai, K
    Lee, SR
    Lo, EH
    [J]. GLIA, 2003, 43 (03) : 254 - 264
  • [2] Specific expression of matrix metalloproteinases 1, 3, 9 and 13 associated with invasiveness of breast cancer cells in vitro
    Balduyck, M
    Zerimech, F
    Gouyer, V
    Lemaire, R
    Hemon, B
    Grard, G
    Thiebaut, C
    Lemaire, V
    Dacquembronne, E
    Duhem, T
    Lebrun, A
    Dejonghe, MJ
    Huet, G
    [J]. CLINICAL & EXPERIMENTAL METASTASIS, 2000, 18 (02) : 171 - 178
  • [3] Matrix metalloproteinase expression in breast cancer
    Bartsch, JE
    Staren, ED
    Appert, HE
    [J]. JOURNAL OF SURGICAL RESEARCH, 2003, 110 (02) : 383 - 392
  • [4] Matrix-metalloproteinases 1, 2 and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions:: an in situ hybridization study
    Brummer, O
    Athar, S
    Riethdorf, L
    Löning, T
    Herbst, H
    [J]. VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 1999, 435 (06): : 566 - 573
  • [5] Expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase-2 in bronchopulmonary and breast lesions
    Caudroy, S
    Polette, M
    Tournier, JM
    Burlet, H
    Toole, B
    Zucker, S
    Birembaut, P
    [J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1999, 47 (12) : 1575 - 1580
  • [6] Chang R, 2002, TECHNOL REV, V105, P16
  • [7] Matrix metalloproteinase abundance in human myocardial fibroblasts: effects of sustained pharmacologic matrix metalloproteinase inhibition
    Chapman, RE
    Scott, AA
    Deschamps, AM
    Lowry, AS
    Stroud, RE
    Ikonomidis, JS
    Spinale, FG
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2003, 35 (05) : 539 - 548
  • [8] Djonov V, 2002, INT J ONCOL, V21, P25
  • [9] Metalloproteinases: role in breast carcinogenesis, invasion and metastasis
    Duffy, MJ
    Maguire, TM
    Hill, A
    McDermott, E
    O'Higgins, N
    [J]. BREAST CANCER RESEARCH, 2000, 2 (04) : 252 - 257
  • [10] Selective growth of human melanoma cells in the brain parenchyma of nude mice
    Fujimaki, T
    Price, JE
    Fan, D
    Bucana, CD
    Itoh, K
    Kirino, T
    Fidler, IJ
    [J]. MELANOMA RESEARCH, 1996, 6 (05) : 363 - 371