Molecular Mechanisms Underlying the Role of Galectin-8 as a Regulator of Cancer Growth and Metastasis

Vinik, Yaron; Shatz-Azoulay, Hadas; Zick, Yehiel

doi:10.4052/tigg.1742.1se

Cited by 11 publications

(15 citation statements)

References 69 publications

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“…In case of the cancer cells, Vinik et al recently concluded that “the evidence, gathered thus far, implicates Gal-8 as a driver of a ‘vicious cycle’, whereby cancer cells that overexpress and secrete Gal-8 benefit from its potential to promote their own growth; potentiate epithelial–mesenchymal transition and induce secretion of metastasis-promoting agents at the metastatic niche that induce further recruitment and seeding of cancer cells. Further in-depth studies related to its mode of action are expected to support ongoing efforts aimed at implementing Gal-8-targeted therapies for the treatment of cancer patients” [ 60 ], an aim becoming a perspective for research on osteoarthritis by the data presented herein. The documented positive correlation between the MS score and immunopositivity is the prerequisite for such a driving-force role of galectin-8.…”

Section: Discussionmentioning

confidence: 98%

Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3

Weinmann

Kenn

Schmidt

et al. 2018

Cell. Mol. Life Sci.

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The reading of glycan-encoded signals by tissue lectins is considered a major route of the flow of biological information in many (patho)physiological processes. The arising challenge for current research is to proceed from work on a distinct protein to family-wide testing of lectin function. Having previously identified homodimeric galectin-1 and chimera-type galectin-3 as molecular switches in osteoarthritis progression, we here provide proof-of-principle evidence for an intra-network cooperation of galectins with three types of modular architecture. We show that the presence of tandem-repeat-type galectin-8 significantly correlated with cartilage degeneration and that it is secreted by osteoarthritic chondrocytes. Glycan-inhibitable surface binding of galectin-8 to these cells increased gene transcription and the secretion of functional disease markers. The natural variant galectin-8 (F19Y) was less active than the prevalent form. Genome-wide array analysis revealed induction of a pro-degradative/inflammatory gene signature, largely under control of NF-κB signaling. This signature overlapped with respective gene-expression patterns elicited by galectins-1 and -3, but also presented supplementary features. Functional assays with mixtures of galectins that mimic the pathophysiological status unveiled cooperation between the three galectins. Our findings shape the novel concept to consider individual galectins as part of a so far not realized teamwork in osteoarthritis pathogenesis, with relevance beyond this disease.Electronic supplementary materialThe online version of this article (10.1007/s00018-018-2856-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 98%

Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3

Weinmann

Kenn

Schmidt

et al. 2018

Cell. Mol. Life Sci.

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“…Galectin-8 plays an important role in normal physiological processes, such as vascular and lymphatic angiogenesis ( Troncoso et al, 2014 ), platelet activation ( Romaniuk et al, 2015 , 2010 ), polarization of T-lymphocytes ( Cárcamo et al, 2006 ), and limb development ( Newman et al, 2018 ). At the same time, galectin-8 is often overexpressed and secreted by some types of tumor cells ( Elola et al, 2014 ; Vinik et al, 2018 ), a phenomenon thought to be crucial to their metastatic ability ( Gentilini et al, 2017 ; Zick et al, 2002 ).…”

Section: Introductionmentioning

confidence: 99%

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Sancho

Chung

et al. 2021

Journal of Cell Science

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The mechanisms underlying the cellular response to extracellular matrices (ECM), consisting of multiple adhesive ligands, are still poorly understood. Here we address this topic by monitoring the differential cellular response to two different extracellular adhesion molecules – fibronectin, a major integrin ligand, and galectin-8, a lectin, that binds β-galactoside residues, as well as to mixtures of the two proteins. Cell spreading on galectin-8 coated substrates results in a larger projected cell area, a more extensive extension of filopodia, yet an inability to form focal adhesions and stress fibers, compared to cell spreading on fibronectin. These differences can be partially reversed by experimental manipulations of small G-proteins of the Rho family and their downstream targets, such as formins, Arp2/3 complex, and Rho kinase. We also show that the physical adhesion of cells to galectin-8 is stronger than the adhesion to fibronectin. Notably, galectin-8 and fibronectin differentially regulate cell spreading and focal adhesion formation, yet they act synergistically to upregulate the number and length of filopodia. The physiological significance of the coherent cellular response to a molecularly complex matrix is discussed.

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“… 28 , 30 , 33 It plays an important role in the control of EC migration, capillary tube formation and in vivo angiogenesis 33 , 46 – 50 and tumour growth. 51 In addition, Gal-8 modulates lymphangiogenesis induced by VEGF-C in vivo and in vitro. 28 , 30 , 33 Nevertheless, to the best of our knowledge, the presence and distribution of Gal-1, -3 and -8, as well as their implications in the pathogenesis of PG, has not been considered.…”

Section: Introductionmentioning

confidence: 99%

Plump endothelial cells integrated into pre-existing venules contribute to the formation of ‘mother’ and ‘daughter’ vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8

Arciniegas

Carrillo

Rojas

et al. 2021

Scars, Burns & Healing

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Introduction: Pyogenic granuloma (PG) is a reactive inflammatory vascular lesion of the skin and mucous membranes, characterised by the presence of enlarged venules and seamed and seamless capillaries with plump endothelial cells (EC), and numerous macrophages. EC activation upregulates the synthesis of galectins and induces their translocation to the EC surface promoting angiogenesis and lymphangiogenesis, particularly galectin-1 (Gal-1), Gal-3 and Gal-8. However, the presence and distribution of Gal-1, -3 and -8, as well as their implications in the pathogenesis of PG, has not been considered. Materials and methods: Eight biopsies from patients diagnosed with PG were selected. The presence of PECAM-1/CD31, IL-1β, VEGF-C, VEGFR-2, VEGFR-3, integrin β1, CD44, fibronectin and Gal-1, -3 and -8 was assessed by immunofluorescence staining using confocal laser scanning microscopy. Results and Discussion: Immunostaining revealed that these molecules were present in the enlarged venules with plump ECs, in some macrophages and other immune cells. We propose that macrophages release VEGF-A and VEGF-C inducing VEGFR-2/VEGFR-3 expression and activation, leading macrophages to transdifferentiate into plump ECs that might integrate into pre-existing venules, contributing to the formation of enlarged venules with transluminal bridges and capillaries. EC activation, induced by certain cytokines, has been shown to stimulate galectin expression and changes in the cellular localisation through association and activation of specific EC surface glycoproteins. Therefore, it is plausible that Gal-1, -3 and -8, acting in a concerted manner, could be mediating the transdifferentiation of macrophages into plump ECs and facilitating their migration and incorporation into the new vessels. Lay Summary In this study, immunostaining of pyogenic granuloma (PG) tissue sections showed immunoreactivity for PECAM-1/CD31, IL-1β, VEGF-C, VEGFR-2 and VEGFR-3, and galectin-1, -3 and -8 in enlarged venules with plump endothelial cells (EC), as well as in some macrophages and other immune cells. Interestingly, enlarged and thin-walled transient vessels lined by PECAM-1/CD31 and VEGFR-2 immunopositive ECs that form from pre-existing normal venules in response to VEGF-A (called ‘mother’ vessels [MV]) and that undergo intraluminal bridging evolving into various types of capillaries (called ‘daughter’ vessels [DV]) have been observed in benign and malignant tumours, in physiological and pathological angiogenesis as well as in vascular malformations, suggesting an important role for VEGF-A and VEGFR-2 in such a process. However, it is not only the mechanisms by which the MVs evolve in different types of DVs that remains to be elucidated, but also whether the cells that form intraluminal bridges proceed from locally activated ECs or whether they are derived from bone marrow precursors or from resident macrophages. Given that the formation of homodimers by Gal-1 and Gal-8 and pentamers by Gal-3 to generate gal–glycan lattices at the cell surface and in the extracellular space has been shown, it is possible that in PG tissue Gal-1, -3 and -8, through their binding partners, form a supramolecular structure at the surface of ECs and plump ECs, macrophages and in the extracellular space that might be mediating the transdifferentiation of macrophages into plump ECs and facilitating the migration and incorporation of these cells into the pre-existing venules, thus contributing to the formation of MVs and DVs.

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Molecular Mechanisms Underlying the Role of Galectin-8 as a Regulator of Cancer Growth and Metastasis

Cited by 11 publications

References 69 publications

Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3

Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3

Differential cellular responses to adhesive interactions with galectin-8- and fibronectin-coated substrates

Plump endothelial cells integrated into pre-existing venules contribute to the formation of ‘mother’ and ‘daughter’ vessels in pyogenic granuloma: possible role of galectin-1, -3 and -8

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