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Clinical & Experimental Metastasis

, Volume 22, Issue 3, pp 237–246 | Cite as

Expression of MMP2, MMP9 and MMP3 in Breast Cancer Brain Metastasis in a Rat Model

  • Odete Mendes
  • Hun-Taek Kim
  • George StoicaEmail author
Article

Abstract

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.

Key words

animal model brain metastasis breast cancer MMP2 MMP3 MMP9 

Abbreviations

BC

breast cancer

BD-IV

BerlinDurkrey

IHC

immunohistochemistry

MMP

matrix metalloproteinases

PBS

phosphate buffered saline

RT-PCR

reverse transcriptase polymerase chain reaction

TIMP

tissue inhibitors of metalloproteinases

WB

Western blotting

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Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Department of Pathobiology, College of Veterinary MedicineTexas A&M UniversityCollege StationUSA

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