Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts

Arad, Uri; Madar-Balakirski, Noa; Angel-Korman, Avital; Sharon, Amir; Tzadok, Sharon; Segal, Ortal; Menachem, Assaf; Gold, Aviram; Elkayam, Ori; Caspi, Dan

doi:10.1016/j.cyto.2015.01.016

Cited by 50 publications

(34 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ACCEPTED MANUSCRIPT 16 promote cell adhesion of tumor cells to stromal cells and to activate survival signaling cascades (20,22,(117)(118)(119)(120)(121). Galectin 3's unique ability to form pentamers with glycoproteins (or glycolipids) allows the protein to help organize molecules on the surface of the plasma membrane.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

165

View full text Add to dashboard Cite

Galectin 3 is a member of a family of β-galactoside binding proteins and has emerged as an important regulator of diverse functions critical in cancer biology including apoptosis, metastasis, immune surveillance, molecular trafficking, mRNA splicing, gene expression, and inflammation. Galectin 3's ability to support cancer cell survival by intra-cellular and extra-cellular mechanisms suggests this molecule is an important component of the tumor microenvironment that potentially could be targeted for therapy. Data is emerging that Galectin 3 is elevated in many cancers including solid tumors and the cancers of the blood. Galectin 3 also appears to be a key molecule produced by tumor microenvironment support cells including mesenchymal stromal cells (MSC) to suppress immune surveillance by killing T cells and interfering with NK cell function and by supporting metastasis. Levels of Galectin 3 increase in the MSC of aging mice and perhaps this contributes to the development of cancer in the elderly. Galectin 3 modulates surface protein expression of a diverse set of glycoproteins including CD44 by regulating endocytosis of these proteins. In addition, Galectin 3 binding to receptor kinases such as CD45 and the T cell receptor is critical in the regulation of their function. In this review I will examine the various mechanisms how Galectin 3 supports chemoresistance and metastasis in solid tumors and in leukemia and lymphoma. I will also discuss possible therapeutic strategies to target this Galectin for cancer therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

show abstract

Section: Accepted Manuscriptmentioning

confidence: 99%

Galectin 3 as a guardian of the tumor microenvironment

Ruvolo

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

175

165

View full text Add to dashboard Cite

show abstract

“…[38][39][40] The rat TMJ synovial tissue expressed TLR-4 and it's the target of LPS, 41 in line with the activation of TLR signalling in synovial fibroblasts that leads to secretion of cytokines, chemokines and matrix-degrading enzymes. [42][43][44][45] Twenty-four hours after injection of CFA into TMJ, chromodacryorrhea in the eyes and intense redness, swelling over the TMJ region and allodynia of inflammatory temporomandibular Joint were observed in all the CFA-injected groups. 31,46 Histopathologic examination showed that the synovial tissues were hypertrophied, with an increase of synoviocytes and infiltrated leukocytes in the CFA-injected TMJ.…”

Section: Rat Temporomandibular Joint Inflammation Induced By Injectiomentioning

confidence: 99%

Synovial TRPV1 is upregulated by 17-β-estradiol and involved in allodynia of inflamed temporomandibular joints in female rats

Hao

Kou

et al. 2015

Archives of Oral Biology

View full text Add to dashboard Cite

“…Even in clinical samples, immunohistochemistry has demonstrated that the expression of galectin-3 is higher in the epithelial layer than in subepithelial connective tissue (56). Galectin-3 is a positive regulator of IL-6 in synoviocytes or fibroblasts (57,58). Since IL-6 induces RANKL in osteoblasts (59,60), it is conceivable that keratinocyte-derived galectin-3 could regulate RANKL expression in fibroblasts through the induction of IL-6.…”

Section: Discussionmentioning

confidence: 99%

Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction

Iwamoto

Nishikawa

Imai

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor B ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. Bone is a highly dynamic organ in which homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. An imbalance between osteoclastic and osteoblastic activity causes various skeletal disorders. Osteoclasts are multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells, which are attracted to the bloodstream by factors, including sphingsine-1 phosphate (1, 2). Osteoclast differentiation and function are regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor B ligand (RANKL) (3-5). Under physiological conditions, osteoblasts or osteocytes are the source of RANKL (6-8). RANKL-mediated osteoclastogenesis also plays an important role in bone destruction in inflammatory bone diseases such as rheumatoid arthritis (RA) or periodontal diseases. In such pathological states, synoviocytes or immune cells, such as B or T lymphocytes, infiltrating into the area are proposed to be the major sources of RANKL (9-11). In RA, infiltration of T helper 17 (Th17) cells is observed in the synovium. Th17 cells indirectly induce RANKL expression in synoviocytes by producing interleukin-17 (IL-17) (12), and Th17 cells themselves express RANKL on their plasma membrane (13). Thus, in many bone destructive diseases, the mechanisms of bone destruction are becoming clarified in detail. However, there are still certain bone destructive diseases whose underlying mechanisms remain to be elucidated. Cholesteatoma, a benign entity arising in temporal bone, is one such disease where our understanding is limited.Cholesteatoma is an epid...

show abstract

Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts

Cited by 50 publications

References 46 publications

Galectin 3 as a guardian of the tumor microenvironment

Galectin 3 as a guardian of the tumor microenvironment

Synovial TRPV1 is upregulated by 17-β-estradiol and involved in allodynia of inflamed temporomandibular joints in female rats

Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction

Contact Info

Product

Resources

About