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Rapid increase in serum levels of matrix metalloproteinase-9 (MMP-9) postoperatively is associated with a decrease in
Avraham Belizon1, Irena Kirman, Moshe Karten
1Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. belizon@nyc.rr.com
Abstract:
We have previously demonstrated a significant decrease in the serum concentration of intact insulin-like growth factor-binding protein (IGFBP-3) after laparotomy. IGFBP-3, a major IGF binding protein, inhibits the growth of tumor cells via several mechanisms. Our goal was to determine, in a murine model, whether matrix metalloproteinase-9 (MMP-9), a known protease of IGFBP-3, is responsible for the postoperative decrease in serum IGFBP-3 levels. Six IGFBP-3 transgenic mice on a CD-1 background were used in this study. These mice over-express human IGFBP-3. Sham laparotomy, in the form of a midline abdominal incision, was the test procedure. General anesthesia was established using ketamine and xylazine immediately before a 30-minute sham laparotomy and before preoperative blood sampling, done via retro-orbital venipuncture, 48 hours before surgery. The animals were sacrificed and blood was drawn 24 hours postoperatively. Plasma MMP-9 activity was measured using zymography at each time point (48 hours before and 24 hours after operation). MMP-9 activity was also measured in mononuclear cell lysates at both time points. Zymography analysis demonstrated significantly higher plasma levels of MMP-9 postoperatively compared with preoperative levels (81 RU vs 40 RU; P < .05). In contrast, mononuclear cell levels of MMP-9 were significantly higher preoperatively compared with postoperative levels (37.5 RU vs. 0.75 RU, P < .05). Plasma levels of MMP-9, a known protease of IGFBP-3, are significantly elevated postoperatively. In addition, mononuclear cells that store MMP-9 are depleted of it postoperatively. This suggests that rapid MMP-9 release by mononuclear cells leads to an increase in serum levels of this protease postoperatively. Further studies will elucidate mechanisms of MMP-9-related IGFBP-3 depletion.
Insights
Postoperative laparotomy increases plasma matrix metalloproteinase-9 (MMP-9) levels, a protease that degrades insulin-like growth factor-binding protein-3 (IGFBP-3). This suggests MMP-9 release contributes to reduced IGFBP-3 after surgery.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Insulin-like growth factor-binding protein-3 (IGFBP-3) inhibits tumor cell growth.
- Serum IGFBP-3 levels significantly decrease after laparotomy.
- Matrix metalloproteinase-9 (MMP-9) is a known protease of IGFBP-3.
Purpose of the Study:
- To investigate if MMP-9 is responsible for the postoperative decrease in serum IGFBP-3 levels.
- To determine MMP-9 activity in plasma and mononuclear cells before and after sham laparotomy in a murine model.
Main Methods:
- Utilized IGFBP-3 transgenic mice overexpressing human IGFBP-3.
- Performed sham laparotomy under general anesthesia.
- Collected blood samples 48 hours preoperatively and 24 hours postoperatively.
- Assessed plasma and mononuclear cell MMP-9 activity using zymography.
Main Results:
- Plasma MMP-9 activity significantly increased postoperatively (81 RU vs. 40 RU; P < .05).
- Mononuclear cell MMP-9 levels significantly decreased postoperatively (37.5 RU vs. 0.75 RU; P < .05).
- Postoperative elevation in plasma MMP-9 correlates with depletion of MMP-9 from mononuclear cells.
Conclusions:
- Postoperative elevation of plasma MMP-9, a protease of IGFBP-3, is observed.
- MMP-9 release from mononuclear cells likely contributes to the decrease in serum IGFBP-3 after surgery.
- Further research is needed to elucidate MMP-9-mediated IGFBP-3 depletion mechanisms.
