Galectins: Multitask signaling molecules linking fibroblast, endothelial and immune cell programs in the tumor microenvironment

Elola, María T.; Ferragut, Fátima; Méndez-Huergo, Santiago P.; Croci, Diego O.; Bracalente, Candelaria; Rabinovich, Gabriel A.

doi:10.1016/j.cellimm.2018.03.008

Cited by 58 publications

(48 citation statements)

References 158 publications

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“…This also holds true for lymphangiogenesis, as Gal-8 potentiates VEGFR3/VEGF-C signaling (Chen et al, 2016). Furthermore, galectins influence the immune compartment by inducing T cell apoptosis, impairing NK function as well as favoring the proliferation of Treg, tolerogenic DC and tumorpromoting macrophages and MDSC (Elola et al, 2018).…”

Section: Tecs and Their Signaling Properties (Angiocrine Factors) Modmentioning

confidence: 95%

“…Glycan-binding endogenous lectins which sustain tumor angiogenesis via autocrine and paracrine signaling (Elola et al, 2018). Directly interact with VEGFR2, bFGF, VEGFR3 and associated with resistance to anti-angiogenic therapies (Markowska et al, 2010;Markowska et al, 2011;Zhao et al, 2011;Laderach et al, 2013;Chen et al, 2016).…”

Section: Galectinsmentioning

confidence: 99%

“…Galectins are a group of glycan-binding endogenous lectin proteins, which show interactions with fibroblasts, endothelial and immune cells. There is growing evidence that several isoforms of this protein family are involved in the function and regulation of the TME (Elola et al, 2018). Accordingly, it has been observed that dysregulated expression of galectins in human tumors is associated with greater extent of vascularization and unfavorable course such as rapid progression and metastatic disease (Liu and Rabinovich, 2005;Laderach et al, 2013).…”

Section: Tecs and Their Signaling Properties (Angiocrine Factors) Modmentioning

confidence: 99%

See 2 more Smart Citations

Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

Nagl

Horvath

Pircher

et al. 2020

Front. Cell Dev. Biol.

120

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Section: Tecs and Their Signaling Properties (Angiocrine Factors) Modmentioning

confidence: 95%

Section: Galectinsmentioning

confidence: 99%

Section: Tecs and Their Signaling Properties (Angiocrine Factors) Modmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

Nagl

Horvath

Pircher

et al. 2020

Front. Cell Dev. Biol.

120

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“…For example, receptors such as CD45 (75) and TIM-3 (76), which are emerging as critical players in healthy immune function and the immune response to cancer, contain prominent mucin domains that are thought to be necessary for their activities. Further, several members of the galectin family, which are prooncogenic glycan-binding proteins, are known mucin binders, but their specificities for discrete glycoproteins have not been fully characterized (77). Enzymatic demucination with StcE could provide a powerful tool for deorphanizing the receptors and ligands that interact with mucin-domain glycoproteins.…”

Section: Stce Cleaves Mucins From Biologicalmentioning

confidence: 99%

The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins

Malaker

Pedram

Ferracane

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

213

284

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Mucin domains are densely O-glycosylated modular protein domains that are found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. Here, we demonstrate that secreted protease of C1 esterase inhibitor (StcE), a bacterial protease from Escherichia coli, cleaves mucin domains by recognizing a discrete peptide-and glycan-based motif. We exploited StcE's unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Finally, using StcE, we discovered that sialic acid-binding Ig-type lectin-7 (Siglec-7), a glycoimmune checkpoint receptor, selectively binds sialomucins as biological ligands, whereas the related receptor Siglec-9 does not. Mucin-selective proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of mucin domain structure and function.O-glycosylation | mucin | protease | glycoproteomics | Siglec

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“…Galectins are another key family of GBPs implicated in virtually all aspects of the immune system (Brinchmann et al, 2018;Elola et al, 2018;Robinson et al, 2019). Galectins are expressed in many cell types including those of squamous epithelia, gastrointestinal tract, adipocytes, immune cells, and even erythrocytes (Thiemann and Baum, 2016).…”

Section: Galectinsmentioning

confidence: 99%

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

et al. 2019

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Glycans and glycan binding proteins (GBPs or lectins) are essential components in almost every aspect of immunology. Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental immunological processes. In order to better study the glycan-GBP interactions, microscope glass slide-based glycan microarrays were conceived and proved to be an incredibly useful and successful tool. A variety of methods have been developed to better present the glycans so that they mimic natural presentations. Breakthroughs in chemical biology approaches have also made available glycans with sophisticated structures that were considered practically impossible just a few decade ago. Glycan microarrays provide a wealth of valuable information in immunological studies. They allow for discovery of detailed glycan binding preferences or novel binding epitopes of known endogenous immune receptors, which can potentially lead to the discovery of natural ligands that carry the glycans. Glycan microarrays also serve as a platform to discover new GBPs that are vital to the process of infection and invasion by microorganisms. This review summarizes the construction strategies and the immunological applications of glycan microarrays, particularly focused on those with the most comprehensive sets of glycan structures. We also review new methods and technologies that have evolved. We believe that glycan microarrays will continue to benefit the growing research community with various interests in the field of immunology.

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Galectins: Multitask signaling molecules linking fibroblast, endothelial and immune cell programs in the tumor microenvironment

Cited by 58 publications

References 158 publications

Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment – New Findings and Future Perspectives

The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

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