The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis

Mark D. Sternlicht, Andre Lochtest, Carolyn J. Sympson, Bing Huey, Jean Philippe Rougier, Joe Gray, Dan Pinkel, Mina J. Bissell, Zena Werb

Research output: Contribution to journalArticle

700 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) are invariably upregulated in the stromal compartment of epithelial cancers and appear to promote invasion and metastasis. Here we report that phenotypically normal mammary epithelial cells with tetracycline-regulated expression of MMP3/stromelysin-1 (Str1) form epithelial glandular structures in vivo without Str1 but form invasive mesenchymal-like tumors with Str1. Once initiated, the tumors become independent of continued Str1 expression. Str1 also promotes spontaneous premalignant changes and malignant conversion in mammary glands of transgenic mice. These changes are blocked by coexpression of a TIMP1 transgene. The premalignant and malignant lesions have stereotyped genomic changes unlike those seen in other murine mammary cancer models. These data indicate that Str1 influences tumor initiation and alters neoplastic risk.

Original languageEnglish (US)
Pages (from-to)137-146
Number of pages10
JournalCell
Volume98
Issue number2
DOIs
StatePublished - Jul 23 1999
Externally publishedYes

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Matrix Metalloproteinase 3
Carcinogenesis
Breast
Peptide Hydrolases
Tumors
Neoplasms
Human Mammary Glands
Tetracycline
Matrix Metalloproteinases
Transgenes
Transgenic Mice
Epithelial Cells
Breast Neoplasms
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Sternlicht, M. D., Lochtest, A., Sympson, C. J., Huey, B., Rougier, J. P., Gray, J., ... Werb, Z. (1999). The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell, 98(2), 137-146. https://doi.org/10.1016/S0092-8674(00)81009-0

The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. / Sternlicht, Mark D.; Lochtest, Andre; Sympson, Carolyn J.; Huey, Bing; Rougier, Jean Philippe; Gray, Joe; Pinkel, Dan; Bissell, Mina J.; Werb, Zena.

In: Cell, Vol. 98, No. 2, 23.07.1999, p. 137-146.

Research output: Contribution to journalArticle

Sternlicht, MD, Lochtest, A, Sympson, CJ, Huey, B, Rougier, JP, Gray, J, Pinkel, D, Bissell, MJ & Werb, Z 1999, 'The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis', Cell, vol. 98, no. 2, pp. 137-146. https://doi.org/10.1016/S0092-8674(00)81009-0
Sternlicht MD, Lochtest A, Sympson CJ, Huey B, Rougier JP, Gray J et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell. 1999 Jul 23;98(2):137-146. https://doi.org/10.1016/S0092-8674(00)81009-0
Sternlicht, Mark D. ; Lochtest, Andre ; Sympson, Carolyn J. ; Huey, Bing ; Rougier, Jean Philippe ; Gray, Joe ; Pinkel, Dan ; Bissell, Mina J. ; Werb, Zena. / The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. In: Cell. 1999 ; Vol. 98, No. 2. pp. 137-146.
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