Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts : a major induction of stromal MMP-13

Lafleur, Marc A., Drew, Angela F., De Sousa, Emma L., Blick, Tony, Bills, Margaret, Walker, Emma C., Williams, Elizabeth D., Waltham, Mark, & Thompson, Erik W. (2005) Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts : a major induction of stromal MMP-13. International Journal of Cancer, 114(4), pp. 544-554.

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In human breast cancer (HBC), as with many carcinoma systems, most matrix metalloproteinases (MMPs) are largely expressed by the stromal cells, whereas the tumour cells are relatively silent in MMP expression. To determine the tissue source of the most relevant MMPs, we xenografted HBC cell lines and HBC tissues into the mammary fat pad (MFP) or bone of immunocompromised mice and measured the expression of human and mouse MMP-2, -9, -11, -13, membrane-type-1 MMP (MT1-MMP), MT2-MMP and MT3-MMP by species-specific real-time quantitative RT-PCR. Our data confirm a stromal origin for most tumour-associated MMPs and indicate marked and consistent upregulation of stromal (mouse) MMP-13 and MT1-MMP in all xenografts studied, irrespective of implantation in the MFP or bone environments. In addition, we show increased expression of both human MMP-13 and human MT1-MMP by the MDA-MB-231 tumour cells grown in the MFP compared to in vitro production. MMP protein and activity data confirm the upregulation of MMP mRNA production and indicate an increase in the activated MMP-2 species as a result of tumour implantation. These data directly demonstrate tumour induction of MMP production by stromal cells in both the MFP and bone environments. These xenografts are a valuable means for examining in vivo production of MMPs and suggest that MMP-13 and MT1-MMP will be relevant targets for inhibiting breast cancer progression.

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ID Code: 72563
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):36 Export Date: 6 May 2014 Source: Scopus PubMed ID: 15551360
Additional URLs:
Keywords: Bone metastasis, Breast tumour, Collagenase-3, Matrix metalloproteinases, Microenvironment, MMP-13, Stroma, Xenograft
DOI: 10.1002/ijc.20763
ISSN: 1097-0215
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 04 Jun 2014 04:15
Last Modified: 04 Jun 2014 04:15

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