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

  • Original Contribution
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Diseases of the Colon & Rectum

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.

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References

To the article

  1. M Braga A Vignali L Gianotti et al. (2002) ArticleTitleLaparoscopic versus open colorectal surgery: a randomized trial on short-term outcome Ann Surg 236 759–66

    Google Scholar 

  2. I Kirman V Cekic N Poltaratskaia et al. (2002) ArticleTitlePlasma 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 change Surgery 132 186–92

    Google Scholar 

  3. ML Cubbage A Suwanichkul DR Powell (1990) ArticleTitleInsulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity J Biol Chem 265 12642–9

    Google Scholar 

  4. MS Lewitt H Saunders JL Phuyal RC Baxter (1994) ArticleTitleComplex formation by human insulin-like growth factor-binding protein-3 and human acid-labile subunit in growth hormone-deficient rats Endocrinology 134 2404–9

    Google Scholar 

  5. B Valentinis A Bhala T DeAngelis R Baserga P Cohen (1995) ArticleTitleThe human insulin-like growth factor (IGF) binding protein-3 inhibits the growth of fibroblasts with a targeted disruption of the IGF-I receptor gene Mol Endocrinol 9 361–7

    Google Scholar 

  6. J Hong G Zhang F Dong MM Rechler (2002) ArticleTitleInsulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells J Biol Chem 277 10489–97

    Google Scholar 

  7. BA Booth M Boes RS Bar (1996) ArticleTitleIGFBP-3 proteolysis by plasmin, thrombin, serum: heparin binding, IGF binding, and structure of fragments Am J Physiol 271 E465–70

    Google Scholar 

  8. SK Durham A Suwanichkul JD Hayes AC Herington DR Powell PG Campbell (1999) ArticleTitleThe heparin binding domain of insulin-like growth factor binding protein (IGFBP)-3 increases susceptibility of IGFBP-3 to proteolysis Horm Metab Res 31 216–25

    Google Scholar 

  9. P Cohen DM Peehl HC Graves RG Rosenfeld (1994) ArticleTitleBiological effects of prostate specific antigen as an insulin-like growth factor binding protein-3 protease J Endocrinol 142 407–15

    Google Scholar 

  10. M Claussen B Kubler M Wendland et al. (1997) ArticleTitleProteolysis of insulin-like growth factors (IGF) and IGF binding proteins by cathepsin D Endocrinology 138 3797–803

    Google Scholar 

  11. A Lemmey P Maddison A Breslin et al. (2001) ArticleTitleAssociation between insulin-like growth factor status and physical activity levels in rheumatoid arthritis J Rheumatol 28 29–34

    Google Scholar 

  12. F Benedetti ParticleDe C Meazza M Oliveri et al. (2001) ArticleTitleEffect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis Endocrinology 142 4818–26

    Google Scholar 

  13. A Grimberg B Liu P Bannerman WS El-Deiry P Cohen (2002) ArticleTitleIGFBP-3 mediates p53-induced apoptosis during serum starvation Int J Oncol 21 327–35

    Google Scholar 

  14. R Rajah B Valentinis P Cohen (1997) ArticleTitleInsulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism J Biol Chem 272 12181–8

    Google Scholar 

  15. KL Leung PB Lai RL Ho et al. (2000) ArticleTitleSystemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma: a prospective randomized trial Ann Surg 231 506–11

    Google Scholar 

  16. F Groof Particlede KF Joosten JA Janssen et al. (2002) ArticleTitleAcute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors J Clin Endocrinol Metab 87 3118–24

    Google Scholar 

  17. A Raynaud-Simon L Perin S Meaume et al. (2002) ArticleTitleIGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy Eur J Endocrinol 146 657–65

    Google Scholar 

  18. AL Crown K Cottle SL Lightman et al. (2002) ArticleTitleWhat is the role of the insulin-like growth factor system in the pathophysiology of cancer cachexia, and how is it regulated? Clin Endocrinol 56 723–33

    Google Scholar 

  19. F Benedetti ParticleDe C Meazza A Martini (2002) ArticleTitleRole of interleukin-6 in growth failure: an animal model Review. Horm Res 58 24–7

    Google Scholar 

  20. T Tsujinaka J Fujita C Ebisui et al. (1996) ArticleTitleInterleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice J Clin Invest 97 244–9

    Google Scholar 

  21. A Gerber A Wille T Welte S Ansorge F Buhling (2001) ArticleTitleInterleukin-6 and transforming growth factor-beta 1 control expression of cathepsins B and L in human lung epithelial cells J Interferon Cytokine Res 21 11–9

    Google Scholar 

  22. JA Solis-Herruzo RA Rippe LW Schrum et al. (1999) ArticleTitleInterleukin-6 increases rat metalloproteinase-13 gene expression through stimulation of activator protein 1 transcription factor in cultured fibroblasts J Biol Chem 274 30919–26

    Google Scholar 

  23. M Yamamoto S Ikeda H Kondo S Inoue (2002) ArticleTitleDesign and synthesis of dual inhibitors for matrix metalloproteinase and cathepsin Bioorg Med Chem Lett 12 375–8

    Google Scholar 

  24. RC Baxter (2001) ArticleTitleSignalling pathways involved in antiproliferative effects of IGFBP-3: a review Mol Pathol 54 145–8

    Google Scholar 

  25. K Yamaguchi Y Takagi S Aoki M Futamura S Saji (2000) ArticleTitleSignificant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection Ann Surg 232 58–65

    Google Scholar 

  26. S Ito H Nakanishi T Hirai et al. (2002) ArticleTitleQuantitative detection of CEA expressing free tumor cells in the peripheral blood of colorectal cancer patients during surgery with real-time RT-PCR on a LightCycler Cancer Lett 183 195–203

    Google Scholar 

  27. 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;275:39146–51

  28. J Hong G Zhang F Dong MM Rechler (2002) ArticleTitleInsulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells J Biol Chem 277 10489–97

    Google Scholar 

To the Authors Reply

  1. F Benedetti ParticleDe C Meazza M Oliveri et al. (2001) ArticleTitleEffect of IL-6 on IGF binding protein-3: a study in IL-6 transgenic mice and in patients with systemic juvenile idiopathic arthritis Endocrinology 142 4818–26

    Google Scholar 

  2. I Kirman V Cekic N Poltaratskaia et al. (2002) ArticleTitlePlasma 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 change Surgery 132 186–92

    Google Scholar 

  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;275:39146–51

  4. J Hong G Zhang F Dong MM Rechler (2002) ArticleTitleInsulin-like growth factor (IGF)-binding protein-3 mutants that do not bind IGF-I or IGF-II stimulate apoptosis in human prostate cancer cells J Biol Chem 277 10489–97

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, New York

    Irena Kirman M.D., Ph.D., Natalia Poltaratskaia M.S., Vesna Cekic R.N., Kenneth A. Forde M.D., Parswa Ansari M.D., Catherine Boulay M.D. & Richard L. Whelan M.D.

Authors
  1. Irena Kirman M.D., Ph.D.
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  2. Natalia Poltaratskaia M.S.
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  3. Vesna Cekic R.N.
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  4. Kenneth A. Forde M.D.
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  5. Parswa Ansari M.D.
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  6. Catherine Boulay M.D.
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  7. Richard L. Whelan M.D.
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Corresponding author

Correspondence to Irena Kirman M.D., Ph.D..

Additional information

Supported by grants from Minimal Access Surgery Center at the New York-Presbyterian Hospital.

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Kirman, I., Poltaratskaia, N., Cekic, V. et al. Depletion of Circulating Insulin-Like Growth Factor Binding Protein 3 After Open Surgery is Associated With High Interleukin-6 Levels. Dis Colon Rectum 47, 911–918 (2004). https://doi.org/10.1007/s10350-004-0512-4

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  • DOI: https://doi.org/10.1007/s10350-004-0512-4

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