A protective role for matrix metalloproteinase-3 in squamous cell carcinoma

Lisa J. McCawley, Howard C. Crawford, Lloyd E. King, John Mudgett, Lynn M. Matrisian

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Elevated expression of matrix metalloproteinase-3 (MMP-3/stromelysin-1) is associated with a variety of tumor types, although its in vivo functional role remains unclear. In human and murine squamous cell carcinoma (SCC), MMP-3 is expressed in the stromal compartment at all of the stages of tumor progression and is expressed by the malignant epithelial cells in late-stage, highly invasive tumors. To elucidate whether MMP-3 plays a causal role during SCC, wild-type and MMP-3 null mice were subjected to chemical carcinogenesis procedures by topical application of either the complete carcinogen 1-methyl-3-nitro-1-nitroso-guanidine or two-stage initiation and promotion with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Contrasting with our expectations, tumors originating on MMP-3 null mice had enhanced initial tumor growth rates as compared with control animals, although there was no difference in tumor onset or incidence. This elevated rate in growth was coupled with an elevated proliferative index and a reduced vasculature density but with no significant effect on apoptosis. Tumors from MMP-3 null mice had a prevalence of undifferentiated spindle tumors as compared with controls, which was concomitant with a higher percentage of MMP-3 null mice evidencing surface lung metastases. Tumor progression in MMP-3 null mice was inversely associated with leukocyte infiltration, in which an overall reduction in tumor-associated macrophages and neutrophils was evident. We propose that MMP-3 is expressed as a protective response and plays an important role in host defense during SCC tumorigenesis.

Original languageEnglish (US)
Pages (from-to)6965-6972
Number of pages8
JournalCancer Research
Volume64
Issue number19
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Matrix Metalloproteinase 3
Matrix Metalloproteinases
Squamous Cell Carcinoma
Neoplasms
Carcinogenesis
Guanidine
Tetradecanoylphorbol Acetate
Growth
Carcinogens
Neutrophils
Leukocytes
Epithelial Cells
Macrophages
Apoptosis
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

McCawley, L. J., Crawford, H. C., King, L. E., Mudgett, J., & Matrisian, L. M. (2004). A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Research, 64(19), 6965-6972. https://doi.org/10.1158/0008-5472.CAN-04-0910

A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. / McCawley, Lisa J.; Crawford, Howard C.; King, Lloyd E.; Mudgett, John; Matrisian, Lynn M.

In: Cancer Research, Vol. 64, No. 19, 01.10.2004, p. 6965-6972.

Research output: Contribution to journalArticle

McCawley, LJ, Crawford, HC, King, LE, Mudgett, J & Matrisian, LM 2004, 'A protective role for matrix metalloproteinase-3 in squamous cell carcinoma', Cancer Research, vol. 64, no. 19, pp. 6965-6972. https://doi.org/10.1158/0008-5472.CAN-04-0910
McCawley LJ, Crawford HC, King LE, Mudgett J, Matrisian LM. A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. Cancer Research. 2004 Oct 1;64(19):6965-6972. https://doi.org/10.1158/0008-5472.CAN-04-0910
McCawley, Lisa J. ; Crawford, Howard C. ; King, Lloyd E. ; Mudgett, John ; Matrisian, Lynn M. / A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. In: Cancer Research. 2004 ; Vol. 64, No. 19. pp. 6965-6972.
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