Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-3 in Localized, Metastasized Prostate Cancer and Benign Prostatic Hyperplasia

Abstract

Objective: Insulin-like growth factors (IGF-I and IGF-II) are important mitogenic peptides and are thought to be significant factors involved in normal and malignant cellular proliferation including benign prostatic hyperplasia (BPH) and prostate cancer (PC). In particular, the association between IGF-I and PC has received much attention. Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier protein in serum for the IGF-I, thus is an important functional modulator of it. On the other hand, one of the functions of prostate-specific antigen (PSA) is to cleave IGFBP-3. Epidemiological studies have shown that decreased levels of serum IGFBP-3 are associated with increased PC risk. Controversial results have also been reported on the value of serum IGF-I and/or IGFBP-3 in the detection of PC, especially of metastatic PC; as increased, decreased or unchanged when compared to BPH. The aim of the present study was to investigate whether serum IGF-I and IGFBP-3 levels change in localized and metastasized PC cases compared with BPH as the control cases. Method: The study included 45 BPH, 24 localized PC and 19 metastasized PC cases. Serum IGF-I and IGFBP-3 levels were measured by two-site immunoradiometric assay kits, and serum total and free PSA levels were assayed by chemiluminescence method. Results: Serum IGF-I levels in both localized and metastasized PC cases were similar to BPH cases (138.3 ± 58.2, 137.7 ± 39.0 and 147.7 ± 44.2 ng/ml, respectively), whereas serum IGFBP-3 levels were lower in metastasized PC group than in BPH group (1,795.6 ± 305.6 and 2,196.0 ± 505.7 ng/ml; p = 0.005). In localized PC, serum IGFBP-3 levels (1,911.00 ± 349.58 ng/ml) were similar to metastasized PC. There were significant correlations between serum IGFBP-3 and serum free PSA in three groups (r = –0.46, p = 0.02 for localized PC; r = –0.56, p = 0.01 for metastasized PC, and r = –0.31, p = 0.03 for BPH). Conclusion: These data reveal that serum IGF-I levels may not change either in localized or metastasized PC, and that decreased serum IGFBP-3 levels may be attributed to its proteolysis by PSA which is increased in PC.