Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice

Tester, A.M., Waltham, M., Oh, S.J., Bae, S.N., Bills, M.M., Walker, E.C., Kern, F.G., Stetler-Stevenson, W.G., Lippman, M.E., & Thompson, E.W. (2004) Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice. Cancer Research, 64(2), pp. 652-658.

View at publisher (open access)


The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents.

Impact and interest:

67 citations in Scopus
Search Google Scholar™
57 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 71831
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Cited By (since 1996):53
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 14744781
Additional URLs:
DOI: 10.1158/0008-5472.CAN-0384-2
ISSN: 1538-7445
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 20 May 2014 03:01
Last Modified: 28 Jan 2015 01:58

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page