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Special Issue "Galectins in Cancer and Translational Medicine"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2017).

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A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Armando Bartolazzi
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Guest Editor
1. Department of Pathology St. Andrea University Hospital, Rome, Italy; Undersecretary of State, Italian Ministry of Health;2. Cellular and Molecular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
Interests: tumor pathology; molecular pathology; cell biology; thyroid cancer; melanoma; solid tumors; molecular targeted therapy; monoclonal antibodies; immunochemistry; immunohistochemistry; galectins; CD44; integrins, adhesion molecules; cell–ECM interactions
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Special Issue Information

Dear Colleagues,

In the post-genomic era, many efforts have been devoted to better understand the biological information encoded by the cell “glycome” in normal and pathologic conditions. The glycan signature of human cells plays a pivotal role in regulating fundamental biological processes, which are critical for cell physiology and for cancer as well.

Galectins (also worded S-type lectins) are an evolutionarily conserved family of endogenous lectins, which bind carbohydrates with high specificity. These molecules, which can be found both intracellularly and in the extracellular milieu, are functionally active in converting glycan-containing information into cell biological programs. This fashionable mechanism of signal transduction plays a relevant role in regulating several biological functions, among which RNA splicing, gene transcription, cell migration and differentiation, apoptosis, immune response and tumor growth and progression.

It is not surprising, indeed, that a large number of studies on galectin–glycan interactions and galectins expression and function in human diseases have been published in the recent literature, spanning from immunology to cardiovascular medicine, from diagnostic Pathology to nuclear medicine.

The aim of this Special Issue of IJMS is to collect selected contributes in the field reporting data, concepts and new ideas, which have the potential to be translated in the clinical setting in a near future, in order to improve the diagnosis and treatment of cancer and other relevant human diseases.

Prof. Dr. Armando Bartolazzi
Guest Editor

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Keywords

  • galectins
  • galectin-1
  • galectin-3
  • galectin-8
  • galectin-9
  • galectins in diagnosis
  • galectins in therapy
  • galectins and immunity
  • galectins and cancer
  • galectins and human diseases

Published Papers (21 papers)

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Editorial

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Open AccessEditorial
Galectins in Cancer and Translational Medicine: From Bench to Bedside
Int. J. Mol. Sci. 2018, 19(10), 2934; https://doi.org/10.3390/ijms19102934 - 27 Sep 2018

Research

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Open AccessArticle
Proteomic Identification of the Galectin-1-Involved Molecular Pathways in Urinary Bladder Urothelial Carcinoma
Int. J. Mol. Sci. 2018, 19(4), 1242; https://doi.org/10.3390/ijms19041242 - 19 Apr 2018
Cited by 3
Abstract
Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In [...] Read more.
Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP+), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival. Full article
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Open AccessArticle
Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin-3: Binding Kinetics and Modeling
Int. J. Mol. Sci. 2018, 19(2), 372; https://doi.org/10.3390/ijms19020372 - 26 Jan 2018
Cited by 9
Abstract
Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and [...] Read more.
Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement in tumor development and proliferation makes this lectin a promising target for early cancer diagnosis and anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids with a high specificity for internal LacNAc epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based oligosaccharide ligands on a scaffold of bovine serum albumin. These neo-glycoproteins rank among the strongest Gal-3 ligands reported, with Kd reaching sub-nanomolar values as determined by surface plasmon resonance. Significant differences in the binding kinetics were observed within the ligand series, showing the tetrasaccharide capped with N,N′-diacetyllactosamine (LacdiNAc) as the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3 carbohydrate recognition domain with docked oligosaccharide ligands is presented that shows the relations in the binding site at the molecular level. The neo-glycoproteins presented herein may be applied for selective recognition of Gal-3 both on the cell surface and in blood serum. Full article
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Open AccessArticle
Overall Survival of Ovarian Cancer Patients Is Determined by Expression of Galectins-8 and -9
Int. J. Mol. Sci. 2018, 19(1), 323; https://doi.org/10.3390/ijms19010323 - 22 Jan 2018
Cited by 4
Abstract
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various implications in cancer biology. In this study, the presence of galectin (Gal)-8 [...] Read more.
The evaluation of new prognostic factors that can be targeted in ovarian cancer diagnosis and therapy is of the utmost importance. Galectins are a family of carbohydrate binding proteins with various implications in cancer biology. In this study, the presence of galectin (Gal)-8 and -9 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining was evaluated using semi-quantitative immunoreactivity (IR) scores and correlated to clinical and pathological data. Different types of galectin expression were compared with respect to disease-free survival (DFS) and overall survival (OS). Gal-8 served as a new positive prognostic factor for the OS and DFS of ovarian cancer patients. Gal-9 expression determined the DFS and OS of ovarian cancer patients in two opposing ways—moderate Gal-9 expression was correlated with a reduced outcome as compared to Gal-9 negative cases, while patients with high Gal-9 expression showed the best outcome. Full article
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Open AccessCommunication
Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models
Int. J. Mol. Sci. 2017, 18(12), 2671; https://doi.org/10.3390/ijms18122671 - 09 Dec 2017
Cited by 9
Abstract
Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in [...] Read more.
Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO2) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1—e.g., by OTX008—may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care. Full article
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Open AccessArticle
Galectins-1, -3, and -7 Are Prognostic Markers for Survival of Ovarian Cancer Patients
Int. J. Mol. Sci. 2017, 18(6), 1230; https://doi.org/10.3390/ijms18061230 - 08 Jun 2017
Cited by 14
Abstract
There is a tremendous need for developing new useful prognostic factors in ovarian cancer. Galectins are a family of carbohydrate binding proteins which have been suggested to serve as prognostic factors for various cancer types. In this study, the presence of Galectin-1, -3, [...] Read more.
There is a tremendous need for developing new useful prognostic factors in ovarian cancer. Galectins are a family of carbohydrate binding proteins which have been suggested to serve as prognostic factors for various cancer types. In this study, the presence of Galectin-1, -3, and -7 was investigated in 156 ovarian cancer specimens by immunochemical staining. Staining was evaluated in the cytoplasm and nucleus of cancer cells as well as the peritumoral stroma using a semi quantitative score (Remmele (IR) score). Patients’ overall survival was compared between different groups of Galectin expression. Galectin (Gal)-1 and -3 staining was observed in the peritumoral stroma as well as the nucleus and cytoplasm of tumor cells, while Gal-7 was only present in the cytoplasm of tumor cells. Patients with Gal-1 expression in the cytoplasm or high Gal-1 expression in the peritumoral stroma showed reduced overall survival. Nuclear Gal-3 staining correlated with a better outcome. We observed a significantly reduced overall survival for cases with high Gal-7 expression and a better survival for Gal-7 negative cases, when compared to cases with low expression of Gal-7. We were able to show that both tumor and stroma staining of Gal-1 could serve as negative prognostic factors for ovarian cancer. We were able to confirm cytoplasmic Gal-7 as a negative prognostic factor. Gal-3 staining in the nucleus could be a new positive prognosticator for ovarian cancer. Full article
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Review

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Open AccessReview
Galectin-3 in Atrial Fibrillation: Mechanisms and Therapeutic Implications
Int. J. Mol. Sci. 2018, 19(4), 976; https://doi.org/10.3390/ijms19040976 - 25 Mar 2018
Cited by 4
Abstract
Maintenance of atrial fibrillation is a complex mechanism, including extensive electrical and structural remodeling of the atria which involves progressive fibrogenesis. Galectin-3 is a biomarker of fibrosis, and, thus, may be involved in atrial remodeling in atrial fibrillation patients. We review the role [...] Read more.
Maintenance of atrial fibrillation is a complex mechanism, including extensive electrical and structural remodeling of the atria which involves progressive fibrogenesis. Galectin-3 is a biomarker of fibrosis, and, thus, may be involved in atrial remodeling in atrial fibrillation patients. We review the role of galectin-3 in AF mechanisms and its potential therapeutic implications. Full article
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Open AccessReview
Galectins as Molecular Targets for Therapeutic Intervention
Int. J. Mol. Sci. 2018, 19(3), 905; https://doi.org/10.3390/ijms19030905 - 19 Mar 2018
Cited by 10
Abstract
Galectins are a family of small, highly conserved, molecular effectors that mediate various biological processes, including chemotaxis and angiogenesis, and that function by interacting with various cell surface glycoconjugates, usually targeting β-galactoside epitopes. Because of their significant involvement in various biological functions and [...] Read more.
Galectins are a family of small, highly conserved, molecular effectors that mediate various biological processes, including chemotaxis and angiogenesis, and that function by interacting with various cell surface glycoconjugates, usually targeting β-galactoside epitopes. Because of their significant involvement in various biological functions and pathologies, galectins have become a focus of therapeutic discovery for clinical intervention against cancer, among other pathological disorders. In this review, we focus on understanding galectin structure-function relationships, their mechanisms of action on the molecular level, and targeting them for therapeutic intervention against cancer. Full article
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Open AccessReview
TrkB-Target Galectin-1 Impairs Immune Activation and Radiation Responses in Neuroblastoma: Implications for Tumour Therapy
Int. J. Mol. Sci. 2018, 19(3), 718; https://doi.org/10.3390/ijms19030718 - 02 Mar 2018
Cited by 2
Abstract
Galectin-1 (Gal-1) has been described to promote tumour growth by inducing angiogenesis and to contribute to the tumour immune escape. We had previously identified up-regulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), the most common extracranial tumour of childhood. While Gal-1 [...] Read more.
Galectin-1 (Gal-1) has been described to promote tumour growth by inducing angiogenesis and to contribute to the tumour immune escape. We had previously identified up-regulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), the most common extracranial tumour of childhood. While Gal-1 did not confer a survival advantage in the absence of exogenous stressors, Gal-1 contributed to enhanced cell migratory and invasive properties. Here, we review these findings and extend them by analyzing Gal-1 mediated effects on immune cell regulation and radiation resistance. In line with previous results, cell autonomous effects as well as paracrine functions contribute to Gal-1 mediated pro-tumourigenic functions. Interfering with Gal-1 functions in vivo will add to a better understanding of the role of the Gal-1 axis in the complex tumour-host interaction during immune-, chemo- and radiotherapy of neuroblastoma. Full article
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Open AccessReview
Galectin-3: The Impact on the Clinical Management of Patients with Thyroid Nodules and Future Perspectives
Int. J. Mol. Sci. 2018, 19(2), 445; https://doi.org/10.3390/ijms19020445 - 02 Feb 2018
Cited by 8
Abstract
Galectins (S-type lectins) are an evolutionarily-conserved family of lectin molecules, which can be expressed intracellularly and in the extracellular matrix, as well. Galectins bind β-galactose-containing glycoconjugates and are functionally active in converting glycan-related information into cell biological programs. Altered glycosylation notably occurring in [...] Read more.
Galectins (S-type lectins) are an evolutionarily-conserved family of lectin molecules, which can be expressed intracellularly and in the extracellular matrix, as well. Galectins bind β-galactose-containing glycoconjugates and are functionally active in converting glycan-related information into cell biological programs. Altered glycosylation notably occurring in cancer cells and expression of specific galectins provide, indeed, a fashionable mechanism of molecular interactions able to regulate several tumor relevant functions, among which are cell adhesion and migration, cell differentiation, gene transcription and RNA splicing, cell cycle and apoptosis. Furthermore, several galectin molecules also play a role in regulating the immune response. These functions are strongly dependent on the cell context, in which specific galectins and related glyco-ligands are expressed. Thyroid cancer likely represents the paradigmatic tumor model in which experimental studies on galectins’ glycobiology, in particular on galectin-3 expression and function, contributed greatly to the improvement of cancer diagnosis. The discovery of a restricted expression of galectin-3 in well-differentiated thyroid carcinomas (WDTC), compared to normal and benign thyroid conditions, contributed also to promoting preclinical studies aimed at exploring new strategies for imaging thyroid cancer in vivo based on galectin-3 immuno-targeting. Results derived from these recent experimental studies promise a further improvement of both thyroid cancer diagnosis and therapy in the near future. In this review, the biological role of galectin-3 expression in thyroid cancer, the validation and translation to a clinical setting of a galectin-3 test method for the preoperative characterization of thyroid nodules and a galectin-3-based immuno-positron emission tomography (immuno-PET) imaging of thyroid cancer in vivo are presented and discussed. Full article
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Open AccessReview
Role of Galectins in Tumors and in Clinical Immunotherapy
Int. J. Mol. Sci. 2018, 19(2), 430; https://doi.org/10.3390/ijms19020430 - 01 Feb 2018
Cited by 18
Abstract
Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse [...] Read more.
Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules. Full article
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Open AccessReview
Dissecting the Structure–Activity Relationship of Galectin–Ligand Interactions
Int. J. Mol. Sci. 2018, 19(2), 392; https://doi.org/10.3390/ijms19020392 - 29 Jan 2018
Cited by 7
Abstract
Galectins are β-galactoside-binding proteins. As carbohydrate-binding proteins, they participate in intracellular trafficking, cell adhesion, and cell–cell signaling. Accumulating evidence indicates that they play a pivotal role in numerous physiological and pathological activities, such as the regulation on cancer progression, inflammation, immune response, and [...] Read more.
Galectins are β-galactoside-binding proteins. As carbohydrate-binding proteins, they participate in intracellular trafficking, cell adhesion, and cell–cell signaling. Accumulating evidence indicates that they play a pivotal role in numerous physiological and pathological activities, such as the regulation on cancer progression, inflammation, immune response, and bacterial and viral infections. Galectins have drawn much attention as targets for therapeutic interventions. Several molecules have been developed as galectin inhibitors. In particular, TD139, a thiodigalactoside derivative, is currently examined in clinical trials for the treatment of idiopathic pulmonary fibrosis. Herein, we provide an in-depth review on the development of galectin inhibitors, aiming at the dissection of the structure–activity relationship to demonstrate how inhibitors interact with galectin(s). We especially integrate the structural information established by X-ray crystallography with several biophysical methods to offer, not only in-depth understanding at the molecular level, but also insights to tackle the existing challenges. Full article
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Open AccessReview
Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z
Int. J. Mol. Sci. 2018, 19(2), 379; https://doi.org/10.3390/ijms19020379 - 26 Jan 2018
Cited by 28
Abstract
Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting [...] Read more.
Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed. Full article
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Open AccessReview
Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives
Int. J. Mol. Sci. 2018, 19(1), 210; https://doi.org/10.3390/ijms19010210 - 10 Jan 2018
Cited by 13
Abstract
The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects [...] Read more.
The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a role in carcinogenesis as recognition patterns for galectins. Galectins are members of the lectin family, which show high affinity for β-galactosides. The galectin–glycan conjugate plays a fundamental role in metastasis, angiogenesis, tumor immunity, proliferation and apoptosis. Galectins’ action is mediated by a structure containing at least one carbohydrate recognition domain (CRD). The potential prognostic value of galectins has been described in several neoplasms and helps clinicians predict disease outcome and determine therapeutic interventions. Currently, new therapeutic strategies involve the use of inhibitors such as competitive carbohydrates, small non-carbohydrate binding molecules and antibodies. This review outlines our current knowledge regarding the mechanism of action and potential therapy implications of galectins in cancer. Full article
Open AccessReview
Galectin-12 in Cellular Differentiation, Apoptosis and Polarization
Int. J. Mol. Sci. 2018, 19(1), 176; https://doi.org/10.3390/ijms19010176 - 07 Jan 2018
Cited by 9
Abstract
Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed [...] Read more.
Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12. Full article
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Open AccessReview
Galectin-7 in Epithelial Homeostasis and Carcinomas
Int. J. Mol. Sci. 2017, 18(12), 2760; https://doi.org/10.3390/ijms18122760 - 19 Dec 2017
Cited by 5
Abstract
Galectins are small unglycosylated soluble lectins distributed both inside and outside the cells. They share a conserved domain for the recognition of carbohydrates (CRD). Although galectins have a common affinity for β-galatosides, they exhibit different binding preferences for complex glycans. First described twenty [...] Read more.
Galectins are small unglycosylated soluble lectins distributed both inside and outside the cells. They share a conserved domain for the recognition of carbohydrates (CRD). Although galectins have a common affinity for β-galatosides, they exhibit different binding preferences for complex glycans. First described twenty years ago, galectin-7 is a prototypic galectin, with a single CRD, able to form divalent homodimers. This lectin, which is mainly expressed in stratified epithelia, has been described in epithelial tissues as being involved in apoptotic responses, in proliferation and differentiation but also in cell adhesion and migration. Most members of the galectins family have been associated with cancer biology. One of the main functions of galectins in cancer is their immunomodulating potential and anti-angiogenic activity. Indeed, galectin-1 and -3, are already targeted in clinical trials. Another relevant function of galectins in tumour progression is their ability to regulate cell migration and cell adhesion. Among these galectins, galectin-7 is abnormally expressed in various cancers, most prominently in carcinomas, and is involved in cancer progression and metastasis but its precise functions in tumour biology remain poorly understood. In this issue, we will focus on the physiological functions of galectin-7 in epithelia and present the alterations of galectin-7 expression in carcinomas with the aim to describe its possible functions in tumour progression. Full article
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Open AccessReview
Galectins and Carcinogenesis: Their Role in Head and Neck Carcinomas and Thyroid Carcinomas
Int. J. Mol. Sci. 2017, 18(12), 2745; https://doi.org/10.3390/ijms18122745 - 18 Dec 2017
Cited by 5
Abstract
Head and neck cancers are among the most frequently occurring cancers worldwide. Of the molecular drivers described for these tumors, galectins play an important role via their interaction with several intracellular pathways. In this review, we will detail and discuss this role with [...] Read more.
Head and neck cancers are among the most frequently occurring cancers worldwide. Of the molecular drivers described for these tumors, galectins play an important role via their interaction with several intracellular pathways. In this review, we will detail and discuss this role with specific reference to galectins-1, -3, and -7 in angiogenesis, cell proliferation, and invasion as well as in cell transformation and cancer progression. Furthermore, we will evaluate the prognostic value of galectin expression in head and neck cancers including those with oral cavity, salivary gland, and nasopharyngeal pathologies. In addition, we will discuss the involvement of these galectins in thyroid cancers where their altered expression is proposed as a new diagnostic biomarker. Full article
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Open AccessReview
Role of Galectins in Multiple Myeloma
Int. J. Mol. Sci. 2017, 18(12), 2740; https://doi.org/10.3390/ijms18122740 - 17 Dec 2017
Cited by 6
Abstract
Galectins are a family of lectins that bind β-galactose-containing glycoconjugates and are characterized by carbohydrate-recognition domains (CRDs). Galectins exploit several biological functions, including angiogenesis, regulation of immune cell activities and cell adhesion, in both physiological and pathological processes, as tumor progression. Multiple myeloma [...] Read more.
Galectins are a family of lectins that bind β-galactose-containing glycoconjugates and are characterized by carbohydrate-recognition domains (CRDs). Galectins exploit several biological functions, including angiogenesis, regulation of immune cell activities and cell adhesion, in both physiological and pathological processes, as tumor progression. Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by the tight adhesion between tumoral PCs and bone marrow (BM) microenvironment, leading to the increase of PC survival and drug resistance, MM-induced neo-angiogenesis, immunosuppression and osteolytic bone lesions. In this review, we explore the expression profiles and the roles of galectin-1, galectin-3, galectin-8 and galectin-9 in the pathophysiology of MM. We focus on the role of these lectins in the interplay between MM and BM microenvironment cells showing their involvement in MM progression mainly through the regulation of PC survival and MM-induced angiogenesis and osteoclastogenesis. The translational impact of these pre-clinical pieces of evidence is supported by recent data that indicate galectins could be new attractive targets to block MM cell growth in vivo and by the evidence that the expression levels of LGALS1 and LGALS8, genes encoding for galectin-1 and galectin-8 respectively, correlate to MM patients’ survival. Full article
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Open AccessReview
Role of Galectin-3 in Bone Cell Differentiation, Bone Pathophysiology and Vascular Osteogenesis
Int. J. Mol. Sci. 2017, 18(11), 2481; https://doi.org/10.3390/ijms18112481 - 21 Nov 2017
Cited by 8
Abstract
Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and [...] Read more.
Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and cartilage matrix mineralization. It was also shown to be highly expressed in differentiating osteoblasts and osteoclasts, in concomitance with expression of osteogenic markers and Runt-related transcription factor 2 and with the appearance of a mature phenotype. Galectin-3 is expressed also by osteocytes, though its function in these cells has not been fully elucidated. The effects of galectin-3 on bone cells were also investigated in galectin-3 null mice, further supporting its role in all stages of bone biology, from development to remodeling. Galectin-3 was also shown to act as a receptor for advanced glycation endproducts, which have been implicated in age-dependent and diabetes-associated bone fragility. Moreover, its regulatory role in inflammatory bone and joint disorders entitles galectin-3 as a possible therapeutic target. Finally, galectin-3 capacity to commit mesenchymal stem cells to the osteoblastic lineage and to favor transdifferentiation of vascular smooth muscle cells into an osteoblast-like phenotype open a new area of interest in bone and vascular pathologies. Full article
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Open AccessReview
Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection
Int. J. Mol. Sci. 2017, 18(10), 2108; https://doi.org/10.3390/ijms18102108 - 08 Oct 2017
Cited by 5
Abstract
The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus [...] Read more.
The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV), hepatitis B virus (HBV), herpes simplex virus (HSV), influenza virus, dengue virus (DENV), and human immunodeficiency virus (HIV). This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases. Full article
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Open AccessReview
Galectin-3 Performance in Histologic and Cytologic Assessment of Thyroid Nodules: A Systematic Review and Meta-Analysis
Int. J. Mol. Sci. 2017, 18(8), 1756; https://doi.org/10.3390/ijms18081756 - 11 Aug 2017
Cited by 14
Abstract
The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was [...] Read more.
The literature on Galectin-3 (Gal-3) was systematically reviewed to achieve more robust information on its histologic reliability in identifying thyroid cancers and on the concordance between Gal-3 test in histologic and cytologic samples. A computer search of the PubMed and Scopus databases was conducted by combinations of the terms thyroid and Gal-3. Initially, 545 articles were found and, after their critical review, 52 original papers were finally included. They reported 8172 nodules with histologic evaluation of Gal-3, of which 358 with also preoperative FNAC Gal-3 assessment. At histology, Gal-3 sensitivity was 87% (95% confidence intervals [CI] from 86% to 88%), and specificity 87% (95% CI from 86% to 88%); in both cases, we found heterogeneity (I2 85% and 93%, respectively) and significant publication bias (p < 0.001). The pooled rate of positive Gal-3 at fine needle aspiration (FNAC) among cancers with histologically proven Gal-3 positivity was 94% (95% CI from 89% to 97%), with neither heterogeneity (I2 14.5%) nor bias (p = 0.086). These data show high reliability of Gal-3 for thyroid cancer at histology, while its sensitivity on FNAC samples is lower. The limits of cytologic preparations and interpretation of Gal-3 results have to be solved. Full article
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