Diseases of the Colon & Rectum

, Volume 47, Issue 6, pp 911–918 | Cite as

Depletion of Circulating Insulin-Like Growth Factor Binding Protein 3 After Open Surgery is Associated With High Interleukin-6 Levels

  • Irena Kirman
  • Natalia Poltaratskaia
  • Vesna Cekic
  • Kenneth A. Forde
  • Parswa Ansari
  • Catherine Boulay
  • Richard L. Whelan
Original Contribution

PURPOSE:

We have previously shown that plasma from open, but not laparoscopic-assisted, surgery patients has increased mitogenic activity for colon cancer cells. Decreased insulin-like growth factor binding protein 3 levels, most likely the result of an open surgery-induced proteolytic activity, may account for this finding. Plasma proteases are activated by interleukin-6. This study was designed to investigate plasma insulin-like growth factor binding protein 3 and interleukin-6 levels after major open or laparoscopic-assisted surgery.

METHODS:

EDTA plasma was obtained from 24 patients undergoing resection for colonic adenocarcinoma. Insulin-like growth factor binding protein 3 was detected by Western blot analysis and enzyme-linked immunosorbent assay. Interleukin-6 levels were determined by enzyme-linked immunosorbent assay. The effect of insulin-like growth factor binding protein 3 on tumor growth was tested using HCT116 cells.

RESULTS:

In patients undergoing open surgery, enzyme-linked immunosorbent assay revealed a significant decrease in total insulin-like growth factor binding protein 3 levels on postoperative Day 1 (915.6 ± 378.5 ng/ml) compared with preoperative levels (1,267.5 ± 407.9 ng/ml; P < 0.001). Western blots revealed a decrease in the levels of intact insulin-like growth factor binding protein 3. In patients undergoing laparoscopic-assisted surgery, levels of total and intact insulin-like growth factor binding protein 3 before surgery (1,088.9 ± 232.5 ng/ml) and on postoperative Day 1 (1,202.3 ± 285.6 ng/ml) were comparable with no significant changes in Western blot analysis. Interleukin-6 levels were undetectable preoperatively. On postoperative Day 1, interleukin-6 concentration was higher in open surgery group (434.8 ± 506.6 pg/ml) compared with laparoscopic-assisted surgery group (100.9 ± 60.2 pg/ml; P < 0.0001), and correlated significantly with a decrease in plasma insulin-like growth factor binding protein 3 after open surgery (r = 0.81; P < 0.0001).

CONCLUSIONS:

A significant decrease in both total and free insulin-like growth factor binding protein 3 occurs after open but not laparoscopic colectomy. There is an associated increase in the levels of interleukin-6. It remains to be proven that the interleukin-6 elevations are responsible for the low insulin-like growth factor binding protein 3 level seen after open surgery.

Keywords

Colon cancer Insulin-like growth factor binding protein 3 Interleukin-6 Surgery 

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To the Authors Reply

  1. 1.
    Benedetti, F, Meazza, C, Oliveri, M,  et al. 2001Effect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritisEndocrinology142481826Google Scholar
  2. 2.
    Kirman, I, Cekic, V, Poltaratskaia, N,  et al. 2002Plasma from patients undergoing major open surgery stimulates in vitro tumor growth: lower insulin-like growth factor binding protein 3 levels may, in part, account for this changeSurgery13218692Google Scholar
  3. 3.
    Fanayan S, Firth SM, Butt AJ, Baxter RC. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta) and the type II TGF-beta receptor. J Biol Chem 200015;275:39146–51Google Scholar
  4. 4.
    Hong, J, Zhang, G, Dong, F, Rechler, MM 2002Insulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cellsJ Biol Chem2771048997Google Scholar

Copyright information

© The American Society of Colon and Rectal Surgeons 2004

Authors and Affiliations

  • Irena Kirman
    • 1
  • Natalia Poltaratskaia
    • 1
  • Vesna Cekic
    • 1
  • Kenneth A. Forde
    • 1
  • Parswa Ansari
    • 1
  • Catherine Boulay
    • 1
  • Richard L. Whelan
    • 1
  1. 1.Department of SurgeryCollege of Physicians and Surgeons of Columbia UniversityNew York

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