Immunohistochemical galectin-3 expression in non-melanoma skin cancers

Kapucuoğlu, Nilgün; Başak, Pınar Yüksel; Bircan, Sema; Sert, Sevda; Akkaya, Vahide Baysal

doi:10.1016/j.prp.2008.09.001

Cited by 26 publications

(30 citation statements)

References 32 publications

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“…It is composed of a short NH 2 terminal domain, which decides specific cellular targets; a repetitive collagen-like sequence, which serves as a substrate for matrix metalloproteinases; and a carboxyl terminal domain that contains the carbohydrate-binding region (Henderson et al, 2006;Mourad-Zeidan et al, 2008). Gal-3 can be expressed in cytoplasm, nucleus, and cell surface, and eventually is secreted into the extracellular matrix and circulation by various cell types, including macrophages and monocytes (Inohara and Raz, 1994;Shibata et al, 2005;Kapucuoglu et al, 2009). A large number of reports show that Gal-3 is mainly secreted by macrophages that mediate chronic and acute inflammation, innate and adaptive immunity, as well as surfactant homeostasis (Reynolds, 2005;MacKinnon et al, 2008).…”

Section: Superstructure and Locationmentioning

confidence: 99%

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Gao

2014

J Pharmacol Exp Ther

217

184

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Fibrotic diseases occur in a variety of organs and lead to continuous organ injury, function decline, and even failure. Currently effective treatment options are limited. Galectin-3 (Gal-3) is a pleiotropic lectin that plays an important role in cell proliferation, adhesion, differentiation, angiogenesis, and apoptosis. Accumulating evidence indicates that Gal-3 activates a variety of profibrotic factors, promotes fibroblast proliferation and transformation, and mediates collagen production. Recent studies have defined key roles for Gal-3 in fibrogenesis in diverse organ systems, including liver, kidney, lung, and myocardial. To help set the stage for future research, we review recent advances about the role played by Gal-3 in fibrotic diseases. Herein we discuss the potential profibrotic role of Gal-3, inhibition of which may represent a promising therapeutic strategy against tissue fibrosis.

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Section: Superstructure and Locationmentioning

confidence: 99%

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Gao

2014

J Pharmacol Exp Ther

217

184

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“…Tumor cells transfected to increase galectin-3 expression have been shown to have higher rate of metastasis compared to control transfectants when inoculated into mice (Bresalier et al, 1998). Galectin-3 expression is variable depending on the cancer studied, even within epithelial neoplasms (Kapucuoglu et al, 2009; Konstantinov et al, 1994; Mollenhauer et al, 2003). In melanoma, galectin-3 tends to be up regulated; however in non-melanoma skin cancers it is down regulated and expression seems to correlate with cell maturity.…”

Section: Roles Of Galectin-3 In Skin Cancersmentioning

confidence: 99%

Galectin-3 and the skin

Larsen

Chen

Saegusa

et al. 2011

Journal of Dermatological Science

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Galectin-3 is highly expressed in epithelial cells including keratinocytes and is involved in the pathogenesis of inflammatory skin diseases by affecting the functions of immune cells. For example, galectin-3 can contribute to atopic dermatitis (AD) by promoting polarization toward a Th2 immune response by regulating dendritic cell (DC) and T cell functions. In addition, galectin-3 may be involved in the development of contact hypersensitivity by regulating the migratory capacity of antigen presenting cells. Galectin-3 may act as a regulator of epithelial tumor progression and development through various signaling pathways, such as inhibiting keratinocyte apoptosis through regulation of the activation status of extracellular signal-regulated kinase (ERK) and activated protein kinase B (AKT). Galectin-3 is detected at different stages of melanoma development. In contrast, a marked decrease in the expression of galectin-3 is observed in non-melanoma skin cancers, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Galectin-3 may play an important role in tumor cell growth, apoptosis, cell motility, invasion, and metastasis. Galectin-3 may be a novel therapeutic target for a variety of skin diseases.

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“…However, increased cell migration on GnT-IIILm332 was not induced by exogenous galectin-3, because modification of Lm332 by GnT-III reduced its ability to bind to galectin-3. These results strongly suggest that galectin-3 may be a cofactor for Lm332-induced cell motility during wound healing and squamous cell carcinoma tumor progression conditions that are associated with GnT-V overexpression (35,36). Therefore, the opposing galectin functions may be attributed to FIGURE 6.…”

Section: Discussionmentioning

confidence: 78%

“…Cytosolic galectin-3 is involved in the regulation of cell proliferation, differentiation, survival, and death (33). Galectin-3 is highly expressed in some cancers, including the human skin cancer squamous cell carcinoma (34,35), and at the leading edge of wound sites (36). Galectin-3 forms a lattice or cell surface microdomain, which links cytokine receptors on the cell surface (37).…”

mentioning

confidence: 99%

Bisecting GlcNAc Residues on Laminin-332 Down-regulate Galectin-3-dependent Keratinocyte Motility

Kariya

Kawamura

Tabei

et al. 2010

Journal of Biological Chemistry

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(2008) J. Biol. Chem. 283, 33036 -33045). However, the underlying molecular mechanism by which GnT-III-Lm332 suppresses the normal biological functions of Lm332 remains to be elucidated. In this study, we show that galectin-3, which is a ␤-galactoside-binding protein, strongly bound to unmodified Lm332 but not to GnT-IIILm332 and that binding of galectin-3 was completely blocked by lactose. Exogenous galectin-3 significantly enhanced keratinocyte cell motility on control Lm332 but not on GnT-III-Lm332. A functional blocking antibody against galectin-3 inhibited Lm332-induced ␣3␤1 and ␣6␤4 integrin clustering and focal contact formation. Co-immunoprecipitation revealed that galectin-3 associated with both ␤4 integrin and epidermal growth factor receptor, thereby cross-linking the two molecules. The associations were inhibited by either the presence of lactose or expression of GnT-III. Moreover, galectin-3 consistently enhanced ERK activation. Taken together, the results of this study are the first to clearly identify the molecular mechanism responsible for the inhibitory effects of GnT-III on extracellular matrix-integrin-meditated cell adhesion, migration, and signal transduction. The findings presented herein shed light on the importance of N-glycosylation-mediated supramolecular complex formation on the cell surface.Tissue maintenance requires that cells be in communication with the surrounding microenvironment. During both physical and pathological conditions, cells receive extracellular matrix (ECM) 2 -mediated signals via cell surface receptors, including cell adhesion, migration, differentiation, and proliferation (1, 2). Significant research effort, using biochemical and genetic techniques, has advanced our understanding of how ECM signals are transduced and then translated into the cell. However, most studies have focused on the protein-protein interactions, namely on ECM-cell surface receptor interactions, rather than on carbohydrate-protein interactions.Laminin-332 (Lm332; previously known as laminin-5) is a component of basement membranes in the skin and other stratified squamous epithelial tissues (2-4). Lm332, which consists of ␣3, ␤3, and ␥2 subunits, associates with hemidesmosomes through integrin ␣6␤4 (5). A null mutation for Lm332 causes a severe and lethal skin blistering disease (6, 7). On the other hand, Lm332 is overexpressed at the leading edge of wounds during healing (8 -10) and in various types of squamous and other epithelial tumors (11,12). In addition, Lm332 plays an essential role in a mouse model of human squamous cell carcinoma tumorigenesis (13). Consistent with the result of in vivo studies, Lm332 promotes various cellular activities in vitro, such as cell adhesion, spreading, migration, and proliferation, via association of the carboxyl-terminal globular domain of the ␣3 chain with cell surface receptors, such as ␣3␤1 integrin, ␣6␤4 integrin, and syndecans (14 -16).Although between 13 and 30% of the total molecular weight of laminins is N-linked glycosylated (17), most studies o...

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Immunohistochemical galectin-3 expression in non-melanoma skin cancers

Cited by 26 publications

References 32 publications

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Functions of Galectin-3 and Its Role in Fibrotic Diseases

Galectin-3 and the skin

Bisecting GlcNAc Residues on Laminin-332 Down-regulate Galectin-3-dependent Keratinocyte Motility

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