IGF-I, insulin and prostate cancer

Abstract

Prostate cancer is the second most frequent malignancy diagnosed in adult men. Androgens are considered the primary growth factors for prostate normal and cancer cells. However, other non-androgenic growth factors are involved in the growth regulation of prostate cancer cells. The association between IGF-I and prostate cancer risk is well established. However, there is no evidence that the measurement of IGF-I enhances the specificity of prostate cancer detection beyond that achievable by serum prostate-specific antigen (PSA) levels. Until now, there is no consensus on the possible association between IGFBP-3 and prostate cancer risk. Although not well established, it seems that high insulin levels are particularly associated with risk of aggressive prostatic tumours. This review describes the physiopathological basis, epidemiological evidence, and animal models that support the association of the IGFs family and insulin with prostate cancer. It also describes the potential therapies targeting these growth factors that, in the future, can be used to treat patients with prostate cancer. RESUMOO câncer de próstata é a segunda neoplasia mais frequentemente diagnosticada em homens adultos. Os androgênios são considerados fatores de crescimento primários para células prostáticas normais e malignas. Entretanto, outros fatores de crescimento não androgênicos estão envolvidos na regulação do crescimento das células prostáticas malignas. Associação entre IGF-I e risco de câncer de próstata é bem estabelecida. No entanto, não há evidência de que a dosagem do IGF-I melhore a especificidade na detecção do câncer de próstata, além daquela alcançada pelos níveis de antígeno prostático específico (PSA). Até hoje, não há consenso sobre a possível associação entre IGFBP-3 e risco de câncer de próstata. Apesar de não estar estabelecido, altos níveis de insulina parecem particularmente associados ao risco de tumores prostáticos agressivos. Esta revisão descreveu base fisiopatológica, evidências epidemiológi-cas e modelos animais que apoiam a associação da família das IGFs e insulina com câncer de próstata. Também foram descritas terapias potenciais que têm como alvo esses fatores de crescimento, os quais, no futuro, poderão ser usados para tratar pacientes com câncer de próstata.Arq Bras Endocrinol Metab. 2009;53(8):969-75

Apigenin Attenuates Insulin-Like Growth Factor-I Signaling in an Autochthonous Mouse Prostate Cancer Model

“…IGF-I is a peptide growth factor that is primarily produced in the liver along with IGF binding protein, IGFBP3 (1, 2). In men with prostate cancer, elevated serum IGF-I levels have been observed at least 5 years prior to the clinical diagnosis of prostate cancer (6).…”

“…IGF-I signaling plays an important role during tumor development and its upregulation has been observed in many human tumors including prostate cancer (1, 2). Epidemiological evidence suggests that patients with elevated serum IGF-I levels in the upper quartile of the reference range had a 4-fold increase risk of developing prostate cancer when compared with patients whose serum IGF-I levels were in the lower quartile (3–5).…”

“…IGF-I and IGF-II; these ligands are primarily synthesized by the liver (1, 2). The biological functions of these ligands are mediated mainly by the IGF-I receptor, which binds IGF-I with higher affinity than IGF-II (2).…”

Precise quantitation of 136 urinary proteins by LC/MRM-MS using stable isotope labeled peptides as internal standards for biomarker discovery and/or verification studies

“…In both parts, the metrics were obtained from peptide standard curves that were prepared and processed on 3 separate days. diagnostic relevance (e.g., protein S100-A9 [56] as well as insulinlike growth factor-binding proteins 1 and 3 [57,58] for prostate cancer, profilin-1 for bladder cancer [59], and C-reactive protein for renal cancer [60]), through non-invasive screening. Nonetheless, the dynamic range of proteins that can be quantified in both biofluids approximates 6 orders using similar processing (includes column loading amounts) and analysis techniques [39,51,61].…”

Leg Length, Body Proportion, Health and Beauty1

“…Raised levels of IGF-I and reduced levels of its main binding protein, insulin-like growth factor (IGF)-binding protein 3, may diminish this defense against a range of cancers". 129, p. 313, citations in the original omitted Since 2001 several more reports of a relationship between IGF-1, IGF-1 receptors and cancer risk have been published, 130,131 as well as associations between IGF-2 and IGF-2 receptors and cancer risk. 132 A search of PubMed.gov using the terms "cancer, IGF" leads to more than 4100 articles published in the past 10 years.…”