Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer
Background. We have previously reported that the glial cell-derived neurotrophic factor
(GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to
determine whether GDNF regulates the expression and activation of matrix
metalloproteinase-9 (MMP-9) in human pancreatic cancer cells. Methods. We used human
pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein
expression was measured by Northern blot, Western blot and enzyme-linked …
(GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to
determine whether GDNF regulates the expression and activation of matrix
metalloproteinase-9 (MMP-9) in human pancreatic cancer cells. Methods. We used human
pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein
expression was measured by Northern blot, Western blot and enzyme-linked …
Background
We have previously reported that the glial cell-derived neurotrophic factor (GDNF) promotes pancreatic cancer cell invasion in vitro. The purpose of this study was to determine whether GDNF regulates the expression and activation of matrix metalloproteinase-9 (MMP-9) in human pancreatic cancer cells.
Methods
We used human pancreatic cancer cell line MIA PaCa-2. The effect of GDNF on mRNA and protein expression was measured by Northern blot, Western blot and enzyme-linked immunosorbent assay. MMP proteolytic activity was detected by gelatin zymography. To determine which intracellular pathways were involved, we used the following inhibitors: tyrosine kinase inhibitor Genistein, MEK-1 inhibitor PD98059 and PI3-K inhibitor Wortmannin.
Results
GDNF increased MMP-9 mRNA and protein expression in MIA PaCa-2 cells in a dose-dependent manner. Treatment with GDNF enhanced gelatinolytic activity of the pro and active form of MMP-9. Inhibitor experiments showed that the expression and activity of pro MMP-9 was totally inhibited by Genistein and partially by Wortmannin, whereas PD98059 had no effect. All three compounds inhibited the activity of the active form of MMP-9.
Conclusions
GDNF upregulates the expression and enzymatic activity of MMP-9 through different signaling pathways in MIA PaCa-2. These findings suggest that GDNF modulates MMP-9 expression and activation, and this may promote pancreatic cancer invasion. (Surgery 2003;134:293-9.)
Elsevier