Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice

William C. Powell, J. David Knox, Marc Navre, Tom M. Grogan, John Kittelson, Raymond B Nagle, G. Tim Bowden

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Human prostate cancer displays a high degree of variability in its rate of spread, which could be due largely to differences in the invasive potential of the tumor cells. The degradation of the basal lamina and stromal extracellular matrix is mediated in part by the secretion of matrix metalloproteinases (MMPs). Matrilysin (PUMP-1, MMP-7) and gelatinase A (Mr 72,000 type IV collagenase, MMP-2) have been shown to be overexpressed in prostate carcinoma. We have expressed the single MMP matrilysin in the tumorigenic but nonmetastatic human prostate tumor cell line DU-145 to determine if matrilysin has a functional role in prostate tumor cell invasion. DU-145 cells expressing matrilysin were significantly more invasive than vector-only transfected cell lines as assayed by a severe combined immunodeficient mouse model of tumor cell invasion. Vectoronly transfected DU-145 cells injected i.p, into severe combined immunodeficient mice invaded the diaphragm in only 1 of 9 mice (11%), whereas matrilysin-transfected DU-145 cells invaded the diaphragm in 12 of 18 mice (66%). The difference between the controls and matrilysin-transtected cells was statistically significant (P < 0.006). These results suggest a functional role for matrilysin in the initial invasion of prostate cancer through the epithelial basal lamina and into the surrounding stroma.

Original languageEnglish (US)
Pages (from-to)417-422
Number of pages6
JournalCancer Research
Volume53
Issue number2
StatePublished - Jan 15 1993

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Matrix Metalloproteinase 7
SCID Mice
Metalloproteases
Prostate
Matrix Metalloproteinase 2
Diaphragm
Matrix Metalloproteinases
Basement Membrane
Prostatic Neoplasms
Neoplasms
Collagenases
Tumor Cell Line
Extracellular Matrix
Carcinoma
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Powell, W. C., Knox, J. D., Navre, M., Grogan, T. M., Kittelson, J., Nagle, R. B., & Bowden, G. T. (1993). Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. Cancer Research, 53(2), 417-422.

Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. / Powell, William C.; Knox, J. David; Navre, Marc; Grogan, Tom M.; Kittelson, John; Nagle, Raymond B; Bowden, G. Tim.

In: Cancer Research, Vol. 53, No. 2, 15.01.1993, p. 417-422.

Research output: Contribution to journalArticle

Powell, WC, Knox, JD, Navre, M, Grogan, TM, Kittelson, J, Nagle, RB & Bowden, GT 1993, 'Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice', Cancer Research, vol. 53, no. 2, pp. 417-422.
Powell, William C. ; Knox, J. David ; Navre, Marc ; Grogan, Tom M. ; Kittelson, John ; Nagle, Raymond B ; Bowden, G. Tim. / Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice. In: Cancer Research. 1993 ; Vol. 53, No. 2. pp. 417-422.
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