Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice

Angus M. Tester, Mark Waltham, Se Jeong Oh, Seog Nyeon Bae, Margaret M. Bills, Emma C. Walker, Francis G. Kern, William G. Stetler-Stevenson, Marc E Lippman, Erik W. Thompson

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)652-658
Number of pages7
JournalCancer Research
Volume64
Issue number2
DOIs
StatePublished - Jan 15 2004
Externally publishedYes

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Matrix Metalloproteinase 2
Matrix Metalloproteinases
Nude Mice
Transfection
Breast Neoplasms
Neoplasm Metastasis
Growth
Clone Cells
Matrix Metalloproteinase 15
Kidney
Bone and Bones
Cell Line
Lung
Matrix Metalloproteinase Inhibitors
Liver
Brain
Concanavalin A
Tumor Burden
Adipose Tissue
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice. / Tester, Angus M.; Waltham, Mark; Oh, Se Jeong; Bae, Seog Nyeon; Bills, Margaret M.; Walker, Emma C.; Kern, Francis G.; Stetler-Stevenson, William G.; Lippman, Marc E; Thompson, Erik W.

In: Cancer Research, Vol. 64, No. 2, 15.01.2004, p. 652-658.

Research output: Contribution to journalArticle

Tester, AM, Waltham, M, Oh, SJ, Bae, SN, Bills, MM, Walker, EC, Kern, FG, Stetler-Stevenson, WG, Lippman, ME & Thompson, EW 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, vol. 64, no. 2, pp. 652-658. https://doi.org/10.1158/0008-5472.CAN-0384-2
Tester, Angus M. ; Waltham, Mark ; Oh, Se Jeong ; Bae, Seog Nyeon ; Bills, Margaret M. ; Walker, Emma C. ; Kern, Francis G. ; Stetler-Stevenson, William G. ; Lippman, Marc E ; Thompson, Erik W. / Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice. In: Cancer Research. 2004 ; Vol. 64, No. 2. pp. 652-658.
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