3958

LGALS3

lectin, galactoside-binding, soluble, 3;LGALS3;lectin, galactoside-binding, soluble, 3

35 kDa lectin|IgE-binding protein|MAC-2 antigen|carbohydrate-binding protein 35|galactose-specific lectin 3|galectin-3|laminin-binding protein|lectin L-29

14q22.3

protein-coding

PURPOSE: Adenoid cystic carcinoma (ACC) is one of the most common malignant tumours of the salivary glands characterized by multiple recurrences and distant metastasis resulting in significantly worsening prognosis. Galectin-3, a member of the beta-galactoside-binding lectin family, has been implicated in tumour progression, metastasis, and found to have prognostic value. The aim of the study was to determine galectin-3 expression in ACC and correlate it with clinicopathological features and patient survival. METHODS: Galectin-3 expression was investigated in paraffin sections of 35 ACC of the head and neck. Patients were divided into two groups based on a threshold of 5% positivity in the tumour cell population. The mean follow-up period for all patients was 90.1 months (range 3-300.1 months). RESULTS: Seventeen (48.6%) tumour specimens were considered galectin-3-positive. Galectin-3 reactivity was significantly associated with regional and distant metastasis (P=0.045 and P<0.001, respectively). There was no statistical significance in the correlation of galectin-3 expression and disease-free survival and overall survival rate (P=0.095 and 0.102, respectively). CONCLUSION: Galectin-3 may be used as an indicator in the prediction of metastatic spread in ACC.

Galectin-3 has been implicated in tumor progression. We demonstrated immunohistochemically that galectin-3 was negative in normal breast tissue, but it was highly increased in breast cancer and in metastatic tissues to brain. Similarly, histochemistry with mucin-specific lectins showed increased recognition in breast tumor and metastasis with Machaerocereus eruca agglutinin (Fualpha 1,2 (GalNAcalpha 1,3) Galss1,4 in complex mucin) but not for Amaranthus leucocarpus (Galss1,3-GalNAc-alpha 1,0-Ser/Thr) and Arachis hypogaea lectins (Galss1,3GalNAc/Galss1,4GlcNAc). Mucin-type glycans and galectin-3 colocalized in breast cancer and metastasis, but not in normal tissue, suggesting upregulated biosynthesis of complex O-glycosidically linked glycans and galectin-3 favor breast cancer progression and brain metastasis.

Galectin-3, beta-galactoside-binding lectin, coats the membrane of most cancer cells and is involved in metastasis and endothelium recognition as well as in evading immune surveillance through killing of activated T cells. To flag galectin as a biomarker of tumours and metastasis, it is pivotal to understand the role of this protein in different tumours and at different stages. Breast tumours have an anomalous behaviour of the galectin-3 compared to other tumour cells. Herein, FACS sorting and galactoside based assays were used to investigate the role of galectin-3 in metastasis and metastatisation of breast cancer cells. Breast galectin fingerprint at the FACS displayed a higher amount in healthy cells, compared to metastatic cells. The microfluidic assay was able to isolate tumour and metastatic cells more than healthy breast cells. Investigation was performed on samples from patients with breast tumours at stage I and stage III whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The readout of the conditioned medium (from culturing of stage I cells) fingerprint by FACS evidenced high expression of free galectin. Analysis of the results established that the galectin coating the membrane, by galactoside recognition of the breast cells, and engaged by the cells to form protein-carbohydrate complexes inside the microfluidic assay, resembled the tumour signature of tumours in breast cells whilst the galectin free is independent of those mechanisms.

OBJECTIVE: To explore the correlation between the expressions of galectin-3 and E-cadherin and lymph node metastasis of colon cancer. METHODS: Immunohistochemistry was employed to examine the expressions of E-cadherin and galectin-3 in 37 colon cancer samples, among which 21 samples underwent RT-PCR for E-cadherin and galectin-3 mRNA expressions. The correlation of E-cadherin and galectin-3 expressions with lymph node metastasis of the tumor was analyzed. RESULTS: The positivity rate of galectin-3 expression was 83.8% (31/37) in these samples. Of the tumor cases with lymph node metastasis, 94.7% (18/19) of the tumors were positive for galectin-3 expression, a rate significantly higher than that in non-metastatic cases. The positivity rate of E-cadherin expression was 59.5% (22/37) in the total cases, and 47.4% (9/19) in the metastatic cases, significantly lower than that in the non-metastatic cases. CONCLUSION: Galectin-3 and E-cadherin expressions are associated with lymph node metastasis of colon cancer and may serve as potential prognostic indicators for colon cancer patients.

INTRODUCTION: Inhibitors of tumor angiogenesis and metastasis are emerging as important new drug candidates for cancer therapy. Galectin-3 and heparanase have been shown to function in tumor progression and metastatic spread. Both of them exert pleiotropic effects; proliferation, cell migration, differentiation and tissue remodeling. The aim of this study was to investigate heparanase and galectin-3 expression in endometrioid and serous carcinomas of the endometrium and their relation with well-known prognostic factors, in addition to estrogen, progesterone, C-erbB-2, Ki-67 and p53. MATERIALS AND METHODS: Sixty-four endometrial cancers, which include 24 serous types, were obtained from previously untreated patients. Immunohistochemical analysis of 64 carcinomas, 20 endometrial hyperplasia (ten of simple hyperplasia and ten of complex atypic hyperplasia) and 20 normal endometrium (ten of proliferative and ten of secretory) was performed. CONCLUSION: This investigation suggests that the decreased expression of galectin-3 may be involved in the pathogenesis of endometrial carcinomas from normal endometrium to carcinoma. Also down-regulated stromal expression of galectin-3 in endometrial carcinoma may be involved in lymph node metastasis. Further studies on a larger advanced stage (FIGO stage 3-4) endometrial carcinoma group may determine the value of heparanase in the endometrial carcinoma.

Lysosome Associated Membrane Protein-1 (LAMP1), which lines the lysosomes, is often found to be expressed on surface of metastatic cells. We previously demonstrated that its surface expression on B16 melanoma variants correlates with metastatic potential. To establish the role of cell surface LAMP1 in metastasis and to understand the possible mechanism by which it facilitates lung colonization, LAMP1 was downregulated in high metastatic B16F10 cells using shRNAs cloned in a doxycycline inducible vector. This also resulted in significantly decreased LAMP1 on the cell surface. Being a major carrier of poly-N-acetyllactosamine (polyLacNAc) substituted beta1,6 branched N-oligosaccharides, the high affinity ligands for galectin-3, LAMP1 down regulation also resulted in appreciably decreased binding of galectin-3 to the cell surface. LAMP1 has been shown to bind to Extracellular Matrix (ECM), Basement Membrane (BM) components and also to galectin-3 (via carbohydrates) which is known to get incorporated into the ECM and BM. Although, LAMP1 downregulation had a marginal effect on cellular spreading and motility on fibronectin and matrigel, it significantly altered the same on galectin-3, and ultimately leading to notably reduced lung metastasis. The results thus for the first time provide direct evidence that cell surface LAMP1 facilitates lung metastasis by providing ligands for galectin-3 which has been shown to be expressed in highest amounts on lungs and constitutively on its vascular endothelium.

Galectin-3, a multifunctional beta-galactocide binding lectin possibly participates in a variety of biological events including cell proliferation, differentiation, and apoptosis. The implication of galectin-3 during malignancy progression has been suggested in several cancers, including colon, prostate, thyroid, and breast cancer, however, scarce data are available in gastric cancer. We examined the expression of galectin-3 in 86 primary gastric cancers and the 40 metastatic lymph nodes by immunohistochemistry to explore whether it is related to the malignant progression. Positive galectin-3 expression was observed in 84% of the gastric cancer cases. In enhanced cells of cancerous lesions, 48% showed stronger nuclear immunoreactivity than cytoplasmic one, whereas adjacent epithelial cells showed little or weak nuclear immunoreactivity. When galectin-3 expression in gastric carcinoma was compared with that in gastric tissues adjacent to the cancers, there was a significant difference. The degree of enhancement of immunoreactivity was different corresponding to various histopathological subtypes in cancer tissues. A significantly stronger expression of galectin-3 in cancer tissues was only observed in papillary and poorly differentiated adenocarcinoma. When galectin-3 expression and tumor progression (TNM staging) was compared, a significant correlation was observed in overall cases, and only in poorly differentiated adenocarcinoma the galectin-3 expression correlated with tumor progression among various subtypes. Galectin-3 expression was observed significantly stronger in metastatic lymph nodes than in the primary gastric cancers, and also in these cases among histological subtypes, only in poorly differentiated adenocarcinoma, the expression of galectin-3 in metastatic lymph nodes was stronger than the primary cancer. In conclusion galectin-3 might be a useful tumor marker for gastric cancers with respects to tumor progression and potentiality of lymph node metastasis especially in certain histological types of gastric cancer.

Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the "protective shield" of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galbeta1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis.

PURPOSE: Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer. EXPERIMENTAL DESIGN: The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3-induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated. RESULTS: Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinalpha(v)beta(1), E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell-endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations. CONCLUSION: The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.

OBJECTIVE: To study the relationship between expression of galectin-3 (Gal-3) and osteopontin (OPN) in occult metastasis in non-small cell lung cancer. METHODS: Forty-six patients of non-small cell lung cancer (NSCLC) from January 2006 to October 2007 were selected. There were 28 males and 18 females, aged from 33 to 77 years old. The levels of lung tissues Gal-3 and OPN were detected by RT-PCR, and the levels of blood plasma's were measured by ELISA. RESULTS: There were 12 patients who had metastasized. In un-metastasis group the Gal-3 and OPN mRNA expression levels were significantly lower than that in metastasis group: mean value were 0.07 +/- 0.17 and 0.17 +/- 0.25 in un-metastasis group, while 0.73 +/- 0.23 and 0.79 +/- 0.24 in metastasis group. Blood plasma levels of Gal-3 (18.8 +/- 7.9) microg/L and OPN (153.5 +/- 63.5) microg/L in NSCLC which were detected from metastasis group were higher than un-metastasis group of (9.2 +/- 5.6) microg/L and (89.2 +/- 24.0) microg/L. CONCLUSIONS: High serum levels of Gal-3 and OPN and high expression of Gal-3 and OPN mRNA in NSCLC are closely related to the occurrence and metastasis of NSCLC. They may be indexes of evaluating the occult metastasis in NSCLC.