1 Biological and immunological properties of insulin-like growth factors (IGF) I and II

Development and differentiation of the mammary gland are dependent on the appropriate temporal expression of both systemically acting hormones and locally produced growth factors. A large body of evidence suggests that molecular crosstalk between these hormonal and growth factor axes is crucial for appropriate cell and tissue function. Two of the most important trophic factors involved in this process are the oestrogen (E) and insulin-like growth factor (IGF) molecular axes. The reciprocal crosstalk that exists between these pathways occurs at transcriptional/post-transcriptional and translational/post-translational levels regulate the expression and activity of genes involved in this process. In a clinical context an important consequence of such crosstalk in the mammary gland is the role which it may play in the aetiology, maintenance and development of breast tumours. Although oestradiol (E₂) acting through oestrogen receptors α and β (ERα/β) is important for normal mammary gland function it can also provide a mitogenic drive to ER + breast tumours. Therefore over several years anti-oestrogen therapeutic regimens in the form of selective oestrogen receptor modulators (SERMs — e.g. tamoxifen), aromatase inhibitors (AI e.g. anastrozole) or selective oestrogen receptor down regulators (SERDs – e.g. fulvestrant) have been used in an adjuvant setting to control tumour growth. Although initial response is usually encouraging, large cohorts of patients eventually develop resistance to these treatments leading to tumour recurrence and poor prognosis. There are potentially many routes by which breast cancer (BC) cells could escape anti-oestrogen based therapeutic strategies and one of the most studied is the possible growth factor mediated activation of ER(s). Because of this, growth factor modulation of ER activity has been an intensively studied route of molecular crosstalk in the mammary gland. The insulin-like growth factors (IGF-1 and -2) are amongst the most potent mitogens for mammary epithelial cells and there is accumulating evidence that they interact with the E₂ axis to regulate mitogenesis, apoptosis, adhesion, migration and differentiation of mammary epithelial cells. Such interactions are bi-directional and E₂ has been shown to regulate the expression and activity of IGF axis genes with the general effect of sensitising breast epithelial cells to the actions of IGFs and insulin. In this short review we discuss the evidence for the involvement of crosstalk between the insulin-like growth factor (IGF) and oestrogen axes in the mammary gland and comment on the relevance of such studies in the aetiology and treatment of BC.

Heparin affinity chromatography has been used to extract minor protein components from two whey protein isolates (WPIs), one produced by ion-exchange chromatography (IEC-WPI) and the second by microfiltration/ultrafiltration (MF/UF-WPI). Only 1–13% of the major whey proteins bound to the heparin column. However, insulin-like growth factor-I (IGF-I), transforming growth factor-beta2 (TGF-β2) and lactoferrin were concentrated by factors of 24–38, 10–0 and 32–93, respectively, in the fraction eluted with 0.5 m NaCl from IEC-WPI and MF/UF-WPI. Two-dimensional gel electrophoresis of this fraction from IEC-WPI (but not from MF/UF-WPI) also revealed the presence of minor proteins, including heart fatty acid-binding protein, transthyretin, β2-microglobulin, and angiogenin. These observations suggest that heparin affinity chromatography can be used not only to separate the major proteins contained in some WPIs, but also to concentrate the minor cationic proteins and some milk growth factors.

The carcass and eating quality of sheep grazing a saltbush dominant saline pasture system or on a ‘control’ dry pasture, stubble plot both supplemented with barley for 14 weeks was investigated (Experiment 1, 50 (2 × 25) 6 month merino lamb wethers and Experiment 2, 50 (2 × 25) 18 month old merino hogget wethers). Treatment had no significant effect on eating quality attributes (P > 0.05). Saltbush grazed sheep in both experiments had a significantly (P < 0.01) lower carcass fat and significantly higher lean (P < 0.01) content than the control grazed sheep. This is a positive finding as fat denudation is a significant cost to processors. The long term consumption of saltbush and barley prior to slaughter did increase muscle fluid content (P < 0.05) but did not result in a decreased carcass weight loss at slaughter due to confounding changes in body composition. Grazing saltbush resulted in increased urine weight (P < 0.001) and decreased urine concentration (P < 0.05) at slaughter indicating an improved hydration status at slaughter. However both experiments demonstrated sub-optimal liveweight gains indicating that saltbush with a barley supplement can still be effectively used as a maintenance ration without compromising carcass and eating quality.

Tendon and ligament injuries are common in athletic horses and can be difficult to treat successfully. Tendons and ligaments are characterized by sparse fibroblasts embedded in a complex structural hierarchy of collagen-rich extracellular matrix (ECM) organized along lines of tension. This precise organizational scheme imparts the necessary mechanical properties for tendons and ligaments to function under high loads. The etiology of tendon and ligament injuries remains the subject of numerous ongoing research projects; however, acute overloading and accumulated microtrauma are the two predominant theories. Under normal physiologic loading, a balance is maintained between the degeneration of ECM and its repair by the resident fibroblast population. When damage occurs faster than it can be repaired, clinical signs of tendonitis or desmitis develop. The molecular and cellular responses that occur during tendon and ligament healing are important to understand, as they provide key points of control that may be targeted for new therapies.