Galectin 3: an extraordinary multifunctional protein in dermatology. Current knowledge and perspectives

Abstract: Galectin 3 is a unique ~31 kDa protein that recognizes the N-acetyl-lactosamine structure of several glycoconjugates. It mainly occurs in epithelial and myeloid cells, but is also found in a variety of human cell types. In view of the crucial role played by galectin 3 in the regulation of cellular processes of essential importance and in the pathogenetic mechanisms of diverse disorders, it is not surprising that, particularly in the last three decades, the attention of the scientific community has been increasingly drawn to this extraordinary and multifunctional galectin. In this paper the authors summarize current knowledge on the expression of galectin 3 in normal and diseased human skin, its implications in the pathogenesis, diagnosis and prognosis of cutaneous disorders, and the perspectives of a novel approach to the treatment of the latter using galectin 3 or its inhibitors/antagonists.

Overexpression of ezrin and galectin-3 as predictors of poor prognosis of cervical cancer

The aim of this study was to explore the correlation of ezrin and galectin-3 expressions with prognosis in cervical cancer. The immunohistochemical method was applied to detect ezrin and galectin-3 expressions in normal cervix tissues (n=30), cervicitis tissues (n=28), cervical intraepithelial neoplasia (CIN) tissues (classified as I-III, n=89), and cervical carcinoma tissues (n=84). Follow-up was conducted for 5 to 78 months to analyze the correlation of protein expressions with prognosis. Ezrin and galectin-3 expressions in cervical cancer were significantly higher than in normal cervix, cervicitis and CIN (all P<0.05), and expressions in CIN were significantly higher than in normal cervix and cervicitis (both P<0.05). The expressions of ezrin and galectin-3 were both related with histological grade, deep myometrial invasion and lymph node metastasis (all P<0.05). Spearman analysis showed that ezrin expression was positively correlated with galectin-3 expression in cervical cancer (r=0.355, P<0.05). The survival rate of patients with high expressions of ezrin and galectin-3 was significantly lower than those with low expressions of proteins (both P<0.05). The expressions of ezrin and galectin-3, histological grade, depth of stromal invasion, and lymph node metastasis are risk factors affecting the survival rate of patients with cervical cancer. The expressions of ezrin and galectin-3 were correlated with the development of cervical cancer, and overexpressions of those proteins were indicative of poor prognosis in patients with cervical cancer.

Metabotropic glutamate receptor 5 may be involved in macrophage plasticity

Abstract Background Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Glutamic acid and glutamate receptors may participate in the regulation of macrophage plasticity. To investigate the role of glutamatergic systems in macrophages physiology, we performed the transfection of mGluR5 cDNAs into RAW-264.7 cells. Results Comparative analysis of modified (RAW-mGluR5 macrophages) and non-modified macrophages (RAW-macrophages) has shown that the RAW-mGluR5 macrophages absorbed more glutamate than control cells and the amount of intracellular glutamate correlated with the expression of excitatory amino acid transporters -2 (EAAT-2). Besides, our results have shown that RAW-mGluR5 macrophages expressed a higher level of peroxisome proliferator-activated receptor γ (PPAR-γ) and secreted more IL-10, high mobility group box 1 proteins (HMGB1) and Galectin-3 than control RAW-macrophages. Conclusions We propose that elevation of intracellular glutamate and expression of mGluR5 may initiate the metabolic rearrangement in macrophages that could contribute to the formation of an immunosuppressive phenotype.

Does diabetes alter immunolocalization of galectin-1 and galectin-3 in the rat ovary? / ¿La diabetes altera la inmunolocalización de galectina-1 y galectina-3 en el ovario de rata?

Diabetes mellitus (DM), is a metabolic disease occurring via insulin secretion deficiency from the pancreas and/or an insufficiency of tissue response to insulin. The present study is intended to show of immunolocalizations of beta-galactose-binding proteins Galectin-1 and Galectin-3 in diabetic rat ovarium and their relationship with diabetes. In this study, 8 to 10-week-old, 250­300 g weighing 50 mature female rats were used, in order to establish diabetes mellitus in those animals, 60 mg/kg intravenous streptozotocin was injected to each animal. After death, diabetics and non-diabetics rats's routine tissue processing steps is done to rat ovarial tissues for immunohistochemical investigation. Strong expressions of Galectin-1 and Galectin-3 were observed in the ovarial germinal epithelium and vascular endothelial. While the strong intense expression of Galectin-1 was seen in the zona pellucida, Galectin-3 expression was strongest in the cytoplesmic regions of cells. Zona pellucida has 3 protein complexes (ZP1, ZP2 and ZP3) in rats and in humans and they have the capability of recognizing the carbonhydrate fields in tissues. The strong expression of galectins in those regions could be the result of carbonhydrate binding properties expression of Gal-3 in the cytoplasmic regions of growing follicles could suggest the idea that Gal-3 could have effects on follicle growth. In conclusion, beta galactose-binding proteins Gal-1 and Gal-3 had stronger immunolocalization in diabetic rat ovarium when compared to the controls. Diabetes could increase the Gal-1 and Gal-3 expressions in the ovarial tissue.

La diabetes mellitus (DM) es una enfermedad metabólica debido a una deficiencia en la secreción de insulina por parte del páncreas o por una insuficiente respuesta de los tejidos a la insulina. El objetivo fue demostrar la inmunolocalización de las proteínas de unión beta-galactosa Galectina-1 y Galectina-3 en los ovarios de ratas diabéticas y su relación con la diabetes. Fueron utilizadas 50 ratas hembras maduras entre 8­10 semanas de edad, con un peso de 250­300 g. Con el fin de desarrollar DM en los animales, se inyectó a cada uno 60 mg/kg de estreptozotocina vía intravenosa. Después de la eutanasia, se realizó el procesamiento de rutina de los tejidos de las ratas diabéticas y no diabéticas para evaluar los tejidos ováricosa través de inmunohistoquímica. Se observaron expresiones fuertes de la Galectina-1 y Galectina-3 en el epitelio germinal y epitelio endotelial vascular del ovario. Si bien la fuerte e intensa expresión de Galectina-1 se observó en la zona pelúcida, la Galectina-3 tuvo una expresión más fuerte en las regiones de las células citoplasmáticas. La zona pelúcida tiene 3 complejos de proteínas (ZP1, ZP2 y ZP3) en ratas y en seres humanos y tienen la capacidad de reconocer los campos de carbohidratos en los tejidos. La fuerte expresión de las galectinas de esas regiones podría ser el resultado de las propiedades de unión a carbonhidratos expresión de Gal-3 en las regiones citoplasmáticas de los folículos en crecimiento, pudiendo sugerir que Gal-3 podría tener efectos sobre el crecimiento del folículo. En conclusión, las proteínas de unión beta-galactosa Gal-1 y Gal-3 tienen una mayor inmunolocalización en los ovarios de ratas diabéticas, en comparación a los controles. La diabetes podría incrementar las expresiones de Gal-1 y Gal-3 en el tejido ovárico.

Diffuse Follicular Variant of Papillary Thyroid Carcinoma in a 69-Year-old Man with Extensive Extrathyroidal Extension: A Case Report

Diffuse follicular variant papillary thyroid carcinoma (DFVPTC) is a rare variant papillary thyroid carcinoma. DFVPTC typically occurs in young females, extensively involves one lobe or both lobes entirely with frequent nodal metastasis and vascular invasion. In contrast to the other subtypes of follicular variant, DFVPTC has biologically aggressive behavior. We present a case of DFVPTC arising in a 69-yr-old male patient. He presented hoarseness for a few months. Following diagnosis of malignancy on aspiration cytology, total thyroidectomy with neck dissection was performed. The tumor involved both lobes of thyroid, encroaching the surrounding structures including tracheal cartilage and esophagus. Multiple lymph node metastasis and vascular invasion were also found. The patient passed away due to the unexplained bleeding of surgical site.

Correlation of Immunohistochemical Markers and BRAF Mutation Status with Histological Variants of Papillary Thyroid Carcinoma in the Korean Population

Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis.

Clinicopathlogic and Immunohistochemical Characteristics of Triple Negative Invasive Lobular Carcinoma

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.

Immunohistochemical localization of galectin-3 in the granulomatous lesions of paratuberculosis-infected bovine intestine

The presence of galectin-3 was immunohistochemically quantified in bovine intestines infected with paratuberculosis (Johne's disease) to determine whether galectin-3 was involved in the formation of granulation tissue associated with the disease. Mycobacterium avium subsp. paratuberculosis infection was histochemically confirmed using Ziehl-Neelsen staining and molecularly diagnosed through rpoB DNA sequencing. Galectin-3 was detected in the majority of inflammatory cells, possibly macrophages, in the granulomatous lesions within affected tissues, including the ileum. These findings suggest that galectin-3 is associated with the formation of chronic granulation tissues in bovine paratuberculosis, probably through cell adhesion and anti-apoptosis mechanisms.

Immunohistochemical study of galectin-3 in mature and immature bull testis and epididymis

Galectin-3, a member of the beta-galactoside-binding protein family, has been implicated in mammalian sperm maturation. We examined galectin-3 expression in the testis and epididymis of sexually mature and immature bulls. Western blot analysis showed varying levels of galectin-3 in the bull testis and epididymis, and galectin-3 immunoreactivity was higher in the mature testis and epididymis than in immature organs. Galectin-3 was primarily localized in interstitial cells of the immature bull testis and in the peritubular myoid and interstitial cells of the mature testis. In the immature epididymis head, galectin-3 was primarily in the principal and basal cells of the epithelium. In the mature epididymis head, moderate levels of galectin-3 were detected in the sperm, while low levels were found in the stereocilia, epithelium and connective tissue. In the immature epididymis body, moderate protein levels were detected in the principal cells, while lower levels were found in the basal cells. The mature epididymis body showed moderate levels of galectin-3 immunostaining in the stereocilia and epithelium, but low levels in the connective tissue. In the immature epididymis tail, only low levels of galectin-3 staining were found in the epithelium, whereas the mature epididymis tail showed high levels of galectin-3 in the principal cells, moderate levels in the basal cells and low levels in connective tissue. These findings suggest that galectin-3 expression plays a role in the maturation and activation of sperm in bulls.

Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms.

Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be expressed in various neoplasms including thyroid tumors. This study was conducted to study the role of galectin-3 in differentiating benign from malignant thyroid nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was performed in 70 cases with adequate smears. The cytology diagnosis of these cases was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20), hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1). Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma was positive but all the cases of medullary carcinoma were negativefor galectin-3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma were positive on cytology and one case offollicular adenoma was also positive. Our study shows that galectin-3 is strongly expressed in smears of papillary carcinoma. However, since it is also expressed in a variety of benign lesions, its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid nodules is limited.