Complexes between insulin-like growth factor binding proteins and alpha-2-macroglobulin in patients with tumor

Šunderić, Miloš; Malenković, Vesna; Nedić, Olgica

doi:10.1016/j.yexmp.2015.03.003

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…The levels of IGFBP-1 may vary depending on the type of tumours. 29 Unfortunately, there was no such information available in this study as only overall cancer has been analysed. Although the mechanisms behind an increased risk of cancer are not known, one may speculate in the regulating role of IGFBP-1 on the growth hormone (GH) axis and cell growth.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort

Ritsinger

Brismar

Mellbin

et al. 2018

Diabetes and Vascular Disease Research

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Section: Discussionmentioning

confidence: 99%

Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort

Ritsinger

Brismar

Mellbin

et al. 2018

Diabetes and Vascular Disease Research

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“…IGF-1 plasma or serum levels have been reported to be increased in patients with a variety of cancers, including colorectal adenoma, malignant melanoma, breast cancer, non-small cell lung cancer [ 4 – 6 ]. However, conflicting results have been observed in studies conducted in prostate cancer, epithelial ovarian cancer, breast cancer, and oral cancer [ 7 – 10 ]. In addition, serum levels of IGFBP-1 have been reported to be increased in metastatic prostate and oral cancers, but not in pancreatic, non-metastatic colorectal or endometrial cancers [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Higher IGFBP-1 to IGF-1 serum ratio predicts unfavourable survival in patients with nasopharyngeal carcinoma

et al. 2017

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BackgroundThe insulin-like growth factor (IGF) system plays an important role in the development and progression of cancer. However, little is known about the expression of the IGF system components and their clinicopathological significance and prognostic value in nasopharyngeal carcinoma (NPC).MethodsIGF system components (IGF-1, IGF-2, IGF-1SR, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-6) were quantified from the plasma of NPC patients and healthy individuals using the RayBio Human Cytokine Antibody Array. IGFBP-1 and IGF-1 mRNA levels were quantified by real-time qPCR, and protein expression was detected by western blot in nine NPC cell lines and four immortalized nasopharyngeal epithelial (NPE) cell lines. Tissue-specific expression of IGFBP-1 and IGF-1 was detected by immunohistochemistry in paraffin-embedded NPC tissues. ELISA analysis was used to measure the serum levels of IGFBP-1 and IGF-1 in 142 NPC patients and 128 healthy controls and determine potential correlation with clinicopathological parameters.ResultsSignificantly higher levels of circulating IGFBP-1 and lower levels of IGF-1 and IGF-2 were detected in NPC patients compared to healthy controls by Cytokine Antibody Array analyses (P = 0.034, 0.012, 0.046, respectively). IGFBP-1 expression was detected in the majority of NPC cell lines, but not in NPE cell lines, and was shown to localize to the nucleus of tumour cells, in contrast to the cytoplasmic staining observed in normal cells. Importantly, IGFBP-1 expression was stronger in NPC tumour tissues compared to peritumoural tissues. In contrast, IGF-1 expression was weak or absent in NPC and NPE cell lines, with the exception of the EBV-infected C666 cell line, and was found to be expressed at lower levels in tumour tissues compared to tumour-adjacent normal tissue. Levels of serum IGFBP-1 were shown to be significantly higher in patients with NPCs compared to healthy control individuals (55.23 ± 41.25 μg/L vs. 32.08 ± 29.73 μg/L, P < 0.001), whereas serum levels of IGF-1 were significantly lower in NPC patients compared to healthy controls (98.14 ± 71.48 μg/L vs. 164.01 ± 92.08 μg/L, P = 0.001). Consistently, the IGFBP-1/IGF-1 serum ratio was shown to be significantly higher in NPC patients compared to healthy control individuals (P = 0.002). Serum levels of IGFBP-1 and the IGFBP-1/IGF-1 ratio significantly correlated with age (P = 0.020; P = 0.016), WHO histological classification (P = 0.044; P = 0.048), titre of EA (EB Virus Capsid Antigen-IgA) and NPC (P = 0.015; P = 0.016). In contrast, higher IGFBP-1 serum levels and IGFBP-1/IGF-1 ratio significantly correlated with poor RFS (P = 0.046; P = 0.037) and OS (P = 0.038; P = 0.009). Multivariate analysis revealed that the IGFBP-1/IGF-1 ratio, but not serum IGFBP-1 level, represents an independent risk factor for poor RFS (P = 0.044) and OS (P = 0.035).ConclusionsA higher IGFBP-1/IGF-1 serum ratio is significantly associated with poor prognosis in NPC patients.

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“…The best known function of α 2 M is its ability to trap covalently a broad spectrum of proteases and facilitate their clearance via interaction with the low-density lipoprotein receptor-related protein (LRP) [ 1 – 3 ]. α 2 M has also been shown to facilitate the clearance of a diverse range of non-covalently bound ligands including the Alzheimer’s disease-associated amyloid β-peptide (Aβ) [ 4 , 5 ] and many cytokines and growth factors [ 6 – 10 ]. The binding of α 2 M to heat-denatured and amyloidogenic peptides and proteins inhibits their aggregation and α 2 M is found co-localized with misfolded proteins in disease states [ 11 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies

et al. 2015

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Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.

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Complexes between insulin-like growth factor binding proteins and alpha-2-macroglobulin in patients with tumor

Cited by 9 publications

References 23 publications

Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort

Elevated levels of insulin-like growth factor-binding protein 1 predict outcome after acute myocardial infarction: A long-term follow-up of the glucose tolerance in patients with acute myocardial infarction (GAMI) cohort

Higher IGFBP-1 to IGF-1 serum ratio predicts unfavourable survival in patients with nasopharyngeal carcinoma

Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies

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