scholarly journals Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers

2018 ◽  
Vol 19 (8) ◽  
pp. 2411 ◽  
Author(s):  
Armando Cevenini ◽  
Stefania Orrù ◽  
Annamaria Mancini ◽  
Andreina Alfieri ◽  
Pasqualina Buono ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Signatures ◽  
Insulin Like Growth Factor ◽  
Cancer Proliferation ◽  
Igf Binding Proteins ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Igf System ◽  
Igf Binding

The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.

Insulin-like growth factor-binding protein-6 and cancer

2012 ◽  
Vol 124 (4) ◽  
pp. 215-229 ◽  
Author(s):  
Leon A. Bach ◽  
Ping Fu ◽  
Zhiyong Yang
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Cancer Therapeutics ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Binding Preference ◽  
Inhibition Of Angiogenesis ◽  
Igf Binding ◽  
Independent Effects

The IGF (insulin-like growth factor) system is essential for physiological growth and it is also implicated in a number of diseases including cancer. IGF activity is modulated by a family of high-affinity IGF-binding proteins, and IGFBP-6 is distinctive because of its marked binding preference for IGF-II over IGF-I. A principal role for IGFBP-6 is inhibition of IGF-II actions, but recent studies have indicated that IGFBP-6 also has IGF-independent effects, including inhibition of angiogenesis and promotion of cancer cell migration. The present review briefly summarizes the IGF system in physiology and disease before focusing on recent studies on the regulation and actions of IGFBP-6, and its potential roles in cancer cells. Given the widespread interest in IGF inhibition in cancer therapeutics, increasing our understanding of the mechanisms underlying the actions of the IGF ligands, receptors and binding proteins, including IGFBP-6, will enhance our ability to develop optimal treatments that can be targeted to the most appropriate patients.

The insulin-like growth factor system in the circulation of patients with viral infections

2004 ◽  
Vol 42 (10) ◽  
Author(s):  
Ivona Baričević ◽  
Olgica Nedić ◽  
Judith Anna Nikolić ◽  
Jasminka Nedeljković
Keyword(s):  
Growth Factor ◽  
Viral Infections ◽  
Serum Cortisol ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Ligand Affinity ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Simplex Virus

AbstractThe insulin-like growth factor (IGF) system was examined in the circulation of patients with viral infections (herpes simplex virus, HSV; cytomegalovirus, CMV; rotavirus, RV and adenovirus, AV). The serum concentrations of IGF-I, IGF-II and cortisol were measured by radioimmunoassay, while IGF-binding proteins (IGFBPs) were characterised by ligand-affinity blotting. Although both IGF-I and IGF-II concentrations were significantly lower in patients with viral infections (p < 0.05) than in healthy persons, the IGF-II/IGF-I ratio was increased (p < 0.05). No correlation between the concentration of IGF-I and IGF-II and the intensity of the antibody response to infection was observed. Ligand-affinity blotting demonstrated decreased amounts of IGFBP-3 (patients with HSV, CMV, AV and some patients with RV), increased IGFBP-2 (some patients with HSV and RV) and IGFBP-1 (patients with RV). Serum cortisol was significantly elevated (p < 0.05) in patients infected with HSV, CMV and RV. The alterations observed can be interpreted as induction of the hypothalamic-pituitary-adrenal axis and suppression of the growth hormone (GH)/IGF axis under the influence of viral infection.

scholarly journals Insulin-like growth factor axis during embryonic development

Reproduction ◽  
2001 ◽  
pp. 31-39 ◽  
Author(s):  
GJ Allan ◽  
DJ Flint ◽  
K Patel
Keyword(s):  
Growth Factor ◽  
Expression Patterns ◽  
Limb Bud ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Type I Igf Receptor ◽  
Igf Binding ◽  
Mrna And Protein Expression

The insulin-like growth factor (IGF) axis has been studied extensively in the developing vertebrate embryo. Knockout experiments have demonstrated that both IGF-I and -II are required for normal development in the mouse embryo, and mRNA and protein expression patterns for both growth factors, together with those for the type I IGF receptor and the six IGF-binding proteins, have been analysed in embryos from different species. Although the unique temporal and spatial expression patterns of these genes indicates important roles for the IGF axis during organ and whole animal development, the variation and complexity of expression makes these roles difficult to unravel. However, one possible mechanism unifying the IGF system in development is programmed cell death (apoptosis), which has been shown to be important in sculpting embryonic tissues, and, in particular, the developing limb bud. In addition, the very early onset of expression of various IGF family members in chicken embryos further emphasizes the fundamental importance of this system in development. This article reviews the work that has been carried out in this area in the context of current understanding of the IGF system.

scholarly journals Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease

2017 ◽  
Vol 102 (9) ◽  
pp. 3526-3534 ◽  
Author(s):  
Ulrick Skipper Espelund ◽  
Mette Bjerre ◽  
Rikke Hjortebjerg ◽  
Torben Riis Rasmussen ◽  
Anders Lundby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pleural Fluid ◽  
Plasma Protein ◽  
Binding Protein ◽  
Protein A ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf Binding ◽  
Stanniocalcin 2 ◽  
Igf Binding Protein

Abstract Context Members of the insulin-like growth factor (IGF) system are primarily produced in the liver and secreted into the circulation, but they are also produced, recruited, and activated locally in tissues. Objective To compare activity and concentrations of IGF system components in pleural fluid and blood. Design Pathological pleural fluid, secondary to lung cancer or nonmalignant disease, and matching blood samples were collected from 24 patients ages 66.7 to 81.9 years. Methods IGF-related proteins and cytokine levels were measured by immunoassays or immunoblotting. Bioactive IGF was measured by an IGF-1 receptor phosphorylation assay. Results Total IGF-1 concentration did not differ between the compartments, but concentrations of free IGF-1 and bioactive IGF were more than threefold higher in pleural fluid than in corresponding serum samples (P = 0.0004), regardless of etiology. Median pregnancy-associated plasma protein-A (PAPP-A) and interleukin (IL)-6 levels were increased 47-fold and 143-fold, respectively, in pleural fluid compared with plasma (P &lt; 0.0001). PAPP-A and IL-6 concentrations correlated positively (r = 0.46; P = 0.02). In pleural fluid, levels of PAPP-A–generated IGF binding protein-4 fragments correlated inversely with that of stanniocalcin-2 (r ≤ −0.42; P ≤ 0.05), a PAPP-A inhibitor; such correlations were absent in plasma. Conclusion Pathological pleural fluid is characterized by increased in vitro IGF bioactivity and elevated concentrations of PAPP-A, an IGF-activating proteinase. Thus, the tissue activity of the IGF system may differ substantially from that of the circulating IGF system. The correlation between IL-6 and PAPP-A indicates that inflammation plays a role in promoting local tissue IGF activity.

Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities

2000 ◽  
Vol 278 (6) ◽  
pp. E967-E976 ◽  
Author(s):  
Robert C. Baxter
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Specific Cell ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Serine Kinase ◽  
Homologous Proteins ◽  
Igf Binding Proteins ◽  
Type I Igf Receptor ◽  
Igf Binding

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of six homologous proteins with high binding affinity for IGF-I and IGF-II. Information from NMR and mutagenesis studies is advancing knowledge of the key residues involved in these interactions. IGF binding may be modulated by IGFBP modifications, such as phosphorylation and proteolysis, and by cell or matrix association of the IGFBPs. All six IGFBPs have been shown to inhibit IGF action, but stimulatory effects have also been established for IGFBP-1, -3, and -5. These generally involve a decrease in IGFBP affinity and may require cell association of the IGFBP, but precise mechanisms are unknown. The same three IGFBPs have well established effects that are independent of type I IGF receptor signaling. IGFBP-1 exerts these effects by signaling through α5β1-integrin, whereas IGFBP-3 and -5 may have specific cell-surface receptors with serine kinase activity. The regulation of cell sensitivity to inhibitory IGFBP signaling may play a role in the growth control of malignant cells.

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