Expression of the metalloproteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice.
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 (M(r) 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. Vector-only 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-transfected 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.
Powell
W C
WC
Department of Radiation Oncology, University of Arizona Medical School, Tucson 85724.
Knox
J D
JD
Navre
M
M
Grogan
T M
TM
Kittelson
J
J
Nagle
R B
RB
Bowden
G T
GT
D000818:Animals; D015153:Blotting, Western; D017364:Collagenases / Q000235:genetics; D003964:Diaphragm / Q000473:pathology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases; D014162:Transfection; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7