Increased Circulating Levels of Galectin Proteins in Patients with Breast, Colon, and Lung Cancer

Galectins are proteins with high-affinity β-galactoside-binding sites that function in a variety of signaling pathways through interactions with glycoproteins. The known contributions of galectins-1, -3, -7, -8, and -9 to angiogenesis, metastasis, cell division, and evasion of immune destruction led us to investigate the circulating levels of these galectins in cancer patients. This study compares galectin concentrations by enzyme-linked immunosorbent assay (ELISA) from each stage of breast, lung, and colon cancer. Galectins-1 and -7, which share a prototype structure, were found to have statistically significant increases in breast and lung cancer. Of the tandem-repeat galectins, galectin-8 showed no statistically significant change in these cancer types, but galectin-9 was increased in colon and lung cancer. Galectin-3 is the only chimera-type galectin and was increased in all stages of breast, colon, and lung cancer. In conclusion, there were significant differences in the galectin levels in patients with these cancers compared with healthy controls, and galectin levels did not significantly change from stage to stage. These findings suggest that further research on the roles of galectins early in disease pathogenesis may lead to novel indications for galectin inhibitors.

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Human small cell lung cancer cells express high affinity naloxone-insensitive [125I]β-endorphin binding sites

Lung Cancer ◽

10.1016/0169-5002(95)98720-u ◽

1995 ◽

Vol 12 (3) ◽

pp. 270

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Binding Sites ◽

Small Cell ◽

Lung Cancer Cells ◽

Small Cell Lung ◽

High Affinity

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A study of the interaction in vitro between type I collagen and a small dermatan sulphate proteoglycan

Biochemical Journal ◽

10.1042/bj2510643 ◽

1988 ◽

Vol 251 (3) ◽

pp. 643-648 ◽

Cited By ~ 57

Author(s):

N Uldbjerg ◽

C C Danielsen

Keyword(s):

Steady State ◽

Binding Sites ◽

Type I Collagen ◽

Enzyme Linked Immunosorbent Assay ◽

Side Chains ◽

Type I ◽

Dermatan Sulphate ◽

Collagen Fibrillogenesis ◽

High Affinity ◽

Sulphate Proteoglycan

The interaction between a small dermatan sulphate proteoglycan isolated from human uterine cervix and collagen type I from human and rat skin was investigated by collagen-fibrillogenesis experiments. Collagen fibrillogenesis was initiated by elevation of temperature and pH after addition of proteoglycan, chondroitinase-digested proteoglycan or isolated side chains, and monitored by turbidimetry. Collagen-associated and unbound proteoglycan was determined by enzyme-linked immunosorbent assay after aggregation was complete. (1) The binding of proteoglycan to collagen could be explained by the presence of two mutually non-interacting binding sites, with Ka1 = 1.3 x 10(8) M-1 and Ka2 = 1.3 x 10(6) M-1. The number of binding sites per tropocollagen molecule was n1 = 0.11 and n2 = 1.1. The 0.1 high-affinity binding site per tropocollagen molecule indicates that the strong interaction between proteoglycan and collagen results from a concerted action of tropocollagen molecules in fibrils. Digestion of the proteoglycan with chondroitinase ABC did not affect these binding characteristics. (2) Proteoglycan did not affect the rate of fibrillogenesis, but increased the steady-state A400 by up to 90%. This increase was directly proportional to the saturation of the high-affinity type of binding sites. Neither isolated core protein nor isolated side chains induced a similar high increase in steady-state A400. (3) Electron micrographs showed that the fibril diameter was affected only to a minor extent, if at all, by the proteoglycan, whereas bundles of laterally aligned fibrils were common in the presence of proteoglycan. (4) Results obtained with human and rat collagen were similar.

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Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Biology ◽

10.3390/biology10080817 ◽

2021 ◽

Vol 10 (8) ◽

pp. 817

Author(s):

Anna Lokshin ◽

Lyudmila M. Mikhaleva ◽

Eugene I. Goufman ◽

Marina N. Boltovskaya ◽

Natalia B. Tikhonova ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Accuracy ◽

Conformational Changes ◽

Operating Characteristic ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Human Plasminogen ◽

Total Psa ◽

Circulating Levels

The differential diagnosis of prostate cancer is problematic due to the lack of markers with high diagnostic accuracy. We previously demonstrated the increased binding of IgG to human plasminogen (PLG) in plasma of patients with prostate cancer (PC) compared to healthy controls. Heavy and light chains of PLG (PLG-H and PLG-L) were immobilized on 96-well plates and the binding of IgG to PLG-H and PLG-L was analyzed in serum from 30 prostate cancer (PC) patients, 30 patients with benign prostatic hyperplasia (BPH) and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that IgG from PC sera bind to PLG-H but not to PLG-L. This interaction occurred through the free IgG C-terminal lysine (Lys) that becomes exposed as a result of IgG conformational changes associated with proteolysis. Circulating levels of modified IgG with exposed C-terminal Lys (IgG-Lys) were significantly higher in PC patients than in healthy controls and in BPH. We used Receiver Operating Characteristic (ROC) analysis to calculate the sensitivity (SN) and specificity (SP) of circulating IgG-Lys for differentiating PC from BPH as 77% and 90%, respectively. The area under the curve (AUC) was 0.87. We demonstrated that the diagnostic accuracy of circulating levels of IgG-Lys is much higher than diagnostic accuracy of total PSA (tPSA).

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The role of galectin-3 and its genetic variants in tumor risk and survival of patients with surgically resected early-stage non-small cell lung cancer

Turkish Journal of Thoracic and Cardiovascular Surgery ◽

10.5606/tgkdc.dergisi.2021.20141 ◽

2021 ◽

Vol 29 (2) ◽

pp. 212-222

Author(s):

Şule Terzioğlu-Uşak ◽

Cem Horozoğlu ◽

Şeyda Demirkol ◽

Akif Turna ◽

İlhan Yaylım

Keyword(s):

Lung Cancer ◽

Confidence Interval ◽

Small Cell Lung Cancer ◽

Patient Group ◽

Cell Lung Cancer ◽

Small Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Gene Variants ◽

Small Cell Lung ◽

Galectin 3

Background: The aim of this study was to investigate the possible relationship between galectin-3 gene variants, serum level, gene expression level, and the risks and survivals of resectable non-small cell lung cancer patients. Methods: The rs4644 and rs4652 variants of galectin-3 were genotyped by TaqMan single nucleotide polymorphism assay using genomic deoxyribonucleic acid isolated from the peripheral blood of 65 (54 males, 11 females; mean age: 60.1±11.9 years; range, 34 to 83 years) with Stage IA-IIIA non-small cell lung cancer who underwent primary surgical treatment and 95 healthy individuals (48 males, 47 females; mean age: 53.9±13.5 years; range, 32 to 87 years) between March 2017 and September 2018. Circulating galectin-3 levels in serum samples of the patient and control groups were assessed by enzyme-linked immunosorbent assay. Messenger ribonucleic acid expression of galectin-3 in tumor and surrounding tissues of the patient group was examined by real-time quantitative polymerase chain reaction. Both predictive and prognostic significance of the results were analyzed. Results: The presence of angiolymphatic invasion was significant in the patients with rs4652 AA genotype (p=0.04). Serum galectin-3 levels were significantly higher in the patients than the controls (p<0.0001). The patients with rs4644 CA/CC (p<0.0001 and p<0.0001) and rs4652 AA/AC (p=0.001 and p<0.0001) genotypes had higher serum galectin-3 levels than their corresponding controls. Serum galectin-3 levels increased in the presence of vascular invasion in patients with both rs4644 AC (p=0.03) and rs4652 AC (p=0.019) genotypes. The receiver operating characteristic curve suggested serum galectin-3 level as a strong predictive marker for the patient group with a cut-off value of 17.089 ng/mL (area under the curve: 0.910±0.04; 95% confidence interval: 0.832-0.988; p<0.001). Univariate analysis revealed the association of lower serum galectin-3 levels with better survival (p=0.048). Multivariate survival analysis showed that only high serum galectin-3 levels tended to be related to survival of the patients (hazard ratio: 5.106; 95% confidence interval: 0.956-27.267; p=0.056). Conclusion: The presence of galectin-3 gene variants may lead to histopathological differences among patients with non-small cell lung cancer. Serum galectin-3 level may be a valuable diagnostic biomarker and be associated with survival of these patients.

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Human small cell lung cancer cells express high affinity naloxone-insensitive [125I]β-endorphin binding sites

Life Sciences ◽

10.1016/0024-3205(94)00960-0 ◽

1994 ◽

Vol 56 (5) ◽

pp. PL97-PL102 ◽

Cited By ~ 1

Author(s):

John E. Taylor

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Binding Sites ◽

Small Cell ◽

Lung Cancer Cells ◽

Small Cell Lung ◽

High Affinity

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Graves Hastalığı ile Tnf- α, Galektin-3 ve Fibronektin Düzeylerinin İlişkisi

The Journal of Tepecik Education and Research Hospital ◽

10.5222/terh.2020.86719 ◽

2020 ◽

Author(s):

Ayşe İrem Yasin ◽

Mahmut Muzaffer İlhan ◽

Saime Turan ◽

İlhan Yaylim ◽

Özcan Karaman ◽

...

Keyword(s):

Inflammatory Process ◽

Tnf Alpha ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Significant Difference ◽

Galectin 3 ◽

Group 2 ◽

The Relationship ◽

Group 1

INTRODUCTION: In the pathogenesis of Graves' disease (GD), which is the most common cause of hyperthyroidism, cellular and humoral immune systems are thought to play a role together. TNF-alpha, fibronectin and galectin-3 known to play an active role in inflammatory processes. The aim of this study was to investigate the relationship between galectin-3, fibronectin and TNF-alpha molecules with hyperthyroidism and GD. METHODS: The study included 108 volunteers, 50 Graves, 19 non-Graves hyperthyroid patients and 39 healthy controls. Galectin-3, fibronectin and TNF-alpha levels measured by enzyme-linked immunosorbent assay (ELISA). In the Graves group (Group 1) 32 women, 18 men; in the non-Graves hyperthyroidism group (Group 2) 13 women, 6 men; and there were age- and sex-matched 26 females and 13 males in the control group (Group 3). RESULTS: TNF-alpha levels were 22.7 ± 1.97 pg / ml in Group 1, 19.8 ± 2.56 pg / ml in Group 2, and 16.6 ± 2.29 pg / ml in the control group. TNF-alpha levels were significantly higher in GD group compared to healthy controls (p <0.009). There was no significant difference between the three groups in terms of galectin-3 and fibronectin levels. DISCUSSION AND CONCLUSION: In this study, the relationship between GD and galectin-3 investigated for the first time in the literature and TNF-alpha levels shown in addition to the inflammatory markers known in GD. This finding supports the previous studies and shows the presence of the inflammatory process in GD. Unlike the other causes of hyperthyroidism, the lightening of this inflammatory process in GD, with inflammatory comorbidities such as ophthalmopathy, orbitopathy and dermopathy, will contribute to the development of new treatment options both for the disease itself and for these comorbidities.

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Establishment of Galectin-3 time-resolved fluoroimmunoassay and its application in idiopathic membranous nephropathy

10.21203/rs.3.rs-816341/v1 ◽

2021 ◽

Author(s):

xiaomei Yu ◽

Lingli Chen ◽

Bo Lin ◽

Li Zhang ◽

Xue Yang ◽

...

Keyword(s):

Correlation Coefficient ◽

Membranous Nephropathy ◽

Idiopathic Membranous Nephropathy ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Time Resolved ◽

Detection Range ◽

Coefficients Of Variation ◽

Sandwich Method ◽

Galectin 3

Abstract Objectives The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum galactose agglutinin 3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. Methods The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated to Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. Results The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85–1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). Conclusions In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. The Gal-3-TRFIA also detected the severity of the IMN course.

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High Affinity Binding Sites for Activated Protein C and Protein C on Cultured Human Umbilical Vein Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648890 ◽

1994 ◽

Vol 72 (03) ◽

pp. 465-474 ◽

Cited By ~ 20

Author(s):

Neelesh Bangalore ◽

William N Drohan ◽

Carolyn L Orthner

Keyword(s):

Binding Sites ◽

Protein C ◽

Umbilical Vein ◽

Activated Protein C ◽

Affinity Binding ◽

Cell Binding ◽

High Affinity Binding ◽

High Affinity ◽

Gla Domain ◽

Umbilical Vein Endothelial Cells

SummaryActivated protein C (APC) is an antithrombotic serine proteinase having anticoagulant, profibrinolytic and anti-inflammatory activities. Despite its potential clinical utility, relatively little is known about its clearance mechanisms. In the present study we have characterized the interaction of APC and its active site blocked forms with human umbilical vein endothelial cells (HUVEC). At 4° C 125I-APC bound to HUVEC in a specific, time dependent, saturable and reversible manner. Scatchard analysis of the binding isotherm demonstrated a Kd value of 6.8 nM and total number of binding sites per cell of 359,000. Similar binding isotherms were obtained using radiolabeled protein C (PC) zymogen as well as D-phe-pro-arg-chloromethylketone (PPACK) inhibited APC indicating that a functional active site was not required. Competition studies showed that the binding of APC, PPACK-APC and PC were mutually exclusive suggesting that they bound to the same site(s). Proteolytic removal of the N-terminal γ-carboxyglutamic acid (gla) domain of PC abolished its ability to compete indicating that the gla-domain was essential for cell binding. Surprisingly, APC binding to these cells appeared to be independent of protein S, a cofactor of APC generally thought to be required for its high affinity binding to cell surfaces. The identity of the cell binding site(s), for the most part, appeared to be distinct from other known APC ligands which are associated with cell membranes or extracellular matrix including phospholipid, thrombomodulin, factor V, plasminogen activator inhibitor type 1 (PAI-1) and heparin. Pretreatment of HUVEC with antifactor VIII antibody caused partial inhibition of 125I-APC binding indicating that factor VIII or a homolog accounted for ∼30% of APC binding. Studies of the properties of surface bound 125I-APC or 125I-PC and their fate at 4°C compared to 37 °C were consistent with association of ∼25% of the initially bound radioligand with an endocytic receptor. However, most of the radioligand appeared not to be bound to an endocytic receptor and dissociated rapidly at 37° C in an intact and functional state. These data indicate the presence of specific, high affinity binding sites for APC and PC on the surface of HUVEC. While a minor proportion of binding sites may be involved in endocytosis, the identity and function of the major proportion is presently unknown. It is speculated that this putative receptor may be a further mechanisms of localizing the PC antithrombotic system to the vascular endothelium.

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