Abstract
Fasting blood samples were obtained before definitive surgery or biopsy in 128 patients referred to the department of surgery with suspected or manifest breast cancer. Insulin-like growth factor (IGF)-I, IGF-II and free IGF-I were measured by radioimmunoassay/immunoradiometric assay, while IGFBP-3 proteolysis was evaluated by Western immunoblot. 12 patients had ductal carcinoma in situ benign conditions, while staging revealed metastatic disease in 15 of 16 patients with invasive cancers. IGFBP-3 proteolysis above the normal range was recorded in 19 patients with invasive cancers, but in none of the patients suffering from DCIS/benign conditions. Increased IGFBP-3 proteolysis was most frequently recorded in patients harbouring large tumours and metastatic disease (Stage I: 0/19, 0%; Stage II: 3/45, 7%, Stage III: 9/37, 24%, and Stage IV: 7/15, 47%). IGFBP-3 proteolysis was significantly higher in Stage III (P =0.01) and IV (P< 0.001) patients compared to the other stage groups (P = 0.001). IGF-I and IGF-II correlated negatively to IGFBP-3 proteolysis and age. Plasma levels of IGF-I and -II were significantly lower in patients with elevated IGFBP-3 proteolysis compared to those within the normal range. Our findings reveal alterations in the IGF-system among a substantial number of patients with large primary breast cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Bereket A, Lang CH, Blethen SL, Fan J, Frost RA and Wilson TA (1995) Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity. J Clin Endocrinol Metab 80: 2282–2288
Blat C, Villaudy J and Binoux M (1994) In vivo proteolysis of serum insulin-like growth factor (IGF) binding protein-3 results in increased availability of IGF to target cells. J Clin Invest 93: 2286–2290
Bruning PF, van Doorn J, Bonfrer JMG, van Noord PAH, Korse CM, Linders TC and Hart AAM (1995) Insulin-like growth factor binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer 62: 266–270
Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH and Pollak M (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279: 563–566
Cotterill AM, Mendel P, Holly JMP, Timmins AG, Camacho-Hubner C, Cwyfan-Hughes S, Ross RMJ, Blum WF and Langford RM (1996) The differential regulation of the circulating levels of the insulin-like growth factors and their binding proteins (IGFBP) 1,2 and 3 after elective abdominal surgery. Clin Endocrinol 44: 91–101
Davies SC, Wass JAH, Ross RJM, Cotterill AM, Buchanan CR, Coulson VJ and Holly JMP (1991) The induction of a specific protease for insulin-like growth factor binding protein-3 in the circulation during severe illness. J Endocrinol 130: 469–473
Frost VJ, Helle SI, Lønning PE, van der Stappen JWJ and Holly JMP (1996) Effects of treatment with megestrol acetate, aminoglutethimide or formestane on insulin-like growth factor (IGF) I and II, IGF-binding proteins (IGFBPs) and IGFBP-3 protease status in patients with advanced breast cancer. J Clin Endocrinol Metab 81: 2216–2221
Guler H-P, Zapf J, Schmid C and Froesch ER (1989) Insulin-like growth factors I and II in healthy man. Estimation of half-lives and production rates. Acta Endocrinol 121: 753–758
Hankinson SE, Willett WE, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE and Pollak M (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351: 1393–1396
Helle SI, Holly JMP, Tally M, Hall K, van der Stappen J and Lønning PE (1996) Influence of treatment with tamoxifen and change in tumour burden on the IGF-system in breast cancer patients. Int J Cancer 69: 335–339
Huynh H, Nickerson T, Pollak M and Yang X (1996) Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780. Clin Cancer Res 2: 2037–2042
Johnson RA and Wichern DW (1982). Applied multivariate statistical analysis,
Jones JI and Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocrine Rev 16: 3–34
Karey KP and Sirbasku DA (1988) Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17β-estradiol. Cancer Res 48: 4083–4092
Peyrat J-P, Bonneterre J, Beuscart R, Djiane J and Demaille A (1988) Insulin-like growth factor receptors in human breast cancer and their relation to estradiol and progesterone receptors. Cancer Res 48: 6429–6433
Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, Lefebvre L and Demaille A (1993) Plasma Insulin-like growth factor-I (IGF-I) concentrations in human breast cancer. Eur J Cancer 29A: 492–497
Resnicoff M, Burgaud J-L, Rotman HL, Abraham D and Baserga R (1995) Correlation between apoptosis, tumorigenesis, and levels of insulin-like growth factor I receptors. Cancer Res 55: 3739–3741
Swenerton KD, Legha SS, Smith T, Hortobagyi GN, Gehan EA, Yap H-Y, Gutterman JU and Blumenschein GR (1979) Prognostic factors in metastatic breast cancer treated with combination chemotherapy. Cancer Res 39: 1552–1562
Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud J-L, Carter D, Baserga R and Glazer PM (1997) Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 57: 3079–3083
Wiseman LR, Johnson MD, Wakeling AE, Lykkesfeldt AE, May FEB and Westley BR (1993) Type I IGF receptor and aquired tamoxifen resistance in oestrogen-responsive human breast cancer cells. Eur J Cancer 29A: 2256–2264
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Helle, S., Geisler, S., Aas, T. et al. Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer. Br J Cancer 85, 74–77 (2001). https://doi.org/10.1054/bjoc.2001.1860
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DOI: https://doi.org/10.1054/bjoc.2001.1860
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