Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mac-2, a galactose-binding lectin secretion by activated macrophages, is the major non-integrin laminin-binding protein in these cells. Mac-2 is also expressed by epithelial cells in the intestine and kidney. We wished to identify intestinal glycoproteins other than laminin that have a high affinity for Mac-2 and that could be considered as candidate ligands or partners for this lectin in intestinal epithelium. Certain lines of human colon adenocarcinoma cells produce two Mac-2-binding glycoproteins (M2BP-1 and M2BP-2) that were identified by their avid association with Mac-2 following detergent lysis and immunoprecipitation. These glycoproteins do not share a common epitope with Mac-2, and the interaction between Mac-2 and these proteins is mediated through the carbohydrate-binding domain of Mac-2 and sugar moieties on M2BP-1 and M2BP-2. M2BP-1 (98 kDa) and M2BP-2 (70 kDa) were purified by immunoaffinity chromatography and were specifically eluted with either galactose or lactose. Peptide maps revealed that M2BP-1 and M2BP-2 are structurally related. M2BP-1 is secreted and could conceivably associate with Mac-2 extracellularly. N-terminal sequence analysis of M2BP-2 suggests that these glycoproteins represent a unique subset of candidate ligands for this mammalian beta-galactoside lectin.
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PMID:Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin. 191 96

Two beta-galactoside-binding proteins were found to be prominently expressed in the human colon adenocarcinoma T84 cell line. Cloning and sequencing of one, a 36-kDa protein, identified it as the human homolog of galectin-4, a protein containing two carbohydrate binding domains and previously found only in the epithelial cells of the rat and porcine alimentary tract. The other, a 29-kDa protein, is galectin-3, containing a single carbohydrate binding domain, previously found in a number of different cell types including human intestinal epithelium. Despite the marked similarities in the carbohydrate binding domains of these two galectins, their cellular distribution patterns are strikingly different and vary with cellular conditions. In confluent T84 cells, galectin-4 is mostly cytosolic and concentrated at the basal membrane, whereas galectin-3 tends to be concentrated in large granular inclusions mostly at the apical membrane. In subconfluent T84 cells, each galectin is distributed to specific domains of lamellipodia, with galectin-4 concentrated in the leading edge and galectin-3 more proximally. Such different localization of galectins-4 and -3 within T84 cells implies different targeting mechanisms, ligands, and functions. The localization of galectin-4 suggests a role in cell adhesion which is also supported by the ability of immobilized recombinant galectin-4 to stimulate adhesion of T84 cells.
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PMID:Strikingly different localization of galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells. Galectin-4 is localized at sites of cell adhesion. 916 64

Lysosomal-membrane-associated glycoproteins (Lamps) 1 and 2 are rarely found on the plasma membranes of normal cells. There is evidence suggesting an increase in their cell-surface expression in tumor cells, with some data indicating that the adhesion of some cancer cells to the extracellular matrix is partly mediated by interactions between Lamps and E-selectin and between Lamps and galectins (endogenous-galactoside-binding lectins). The present study examined the expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in different human tumor cell lines. Indirect immunofluorescence staining revealed accumulation of Lamp molecules at the edges of A2058 human metastasizing melanoma cells suggesting that these glycoproteins could participate in cell adhesion. Flow cytometry showed the presence of cell-surface Lamps in A2058, HT1080 (human fibrosarcoma) and CaCo-2 (human colon-adenocarcinoma) cells. Treatment with 2 mM sodium butyrate for 24 and 48 hr resulted in a significant increase in Lamps surface expression. A strong binding of A2058 to recombinant galectin-3 was detected by FACS. The application of 2 and 5 mM butyrate for the same incubation period enhanced galectin-3 binding to Lamps-expressing cells. Our results support the idea that Lamps may be considered a new family of adhesive glycoproteins participating in the complex process of tumor invasion and metastasis.
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PMID:Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells. 942 97

Galectin-1 and galectin-3, two beta-galactoside-binding proteins, have been suggested to play a role in the development and progression of cancer. We have studied the expression of these molecules in normal human prostate tissue and prostate adenocarcinoma. Immunohistochemistry was used to examine formalin-fixed, paraffin-embedded sections of seven normal human prostates, eight cases of prostatic intraepithelial neoplasia (PIN), 20 primary adenocarcinomas of the prostate, and 12 prostate cancer metastases. Galectin-1 was expressed in most cases of all four histologic types. In contrast, galectin-3 expression was significantly decreased in primary carcinoma and metastatic disease compared with normal and premalignant tissue. Galectin-3 expression in primary tumors tended to be less than that of surrounding normal glands. We conclude that loss of galectin-3 expression may be associated with the progression of prostate cancer.
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PMID:Galectin-1 and galectin-3 expression in human prostate tissue and prostate cancer. 1055 May 25

Galectin-3 is a lactosamine-specific lectin that binds to laminin sugar-sites, and up-regulated expression of galectin-3 in primary colorectal cancer is involved in cancer progression and metastasis. Inhibitory effects of cell adhesion and liver metastasis of adenocarcinoma via portal vein by lectin-binding sugar and anti-galectin-3 antibody was examined to determine the role of galectin-laminin binding in cancer liver metastasis. Highly metastatic adenocarcinoma cell lines XK4-A3 and RPMI4788 were used in in vitro cell attachment and nude mice liver metastatic experiments, and inhibitory effects of anti-galectin-3 antibody or lectin-binding sugars were examined. The in vitro adhesion assay demonstrated that the anti-galectin-3 antibody and alpha-lactose inhibited XK4-A3 and RPMI4788 cell adhesion to laminin in a dose-dependent manner. The liver metastasis of XK4-A3 and RPMI4788 was reduced 50 and 60%, respectively (P<0.001) by alpha-lactose treatment. Anti-galectin-3 antibody also inhibited liver metastasis in a dose-dependent manner, and maximum inhibition rate was 66% for XK4-A3 and 90% for RPMI4788. Galectin-3 plays an important role in liver metastasis of adenocarcinoma by the mechanisms of galectin-3 binding to laminin. Inhibition of galectin-3 on cancer cell surface induces reduced cell attachment to laminin and liver metastasis.
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PMID:Role of galectin-3 in adenocarcinoma liver metastasis. 1160 88

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin beta-galactosidase-binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffin-embedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1+ (5-25% positive), 2+ (26-50% positive), or 3+ (>50% positive). C-kit was expressed by 100% of ACC (3+: 7 cases; 2+: 1 case; 1+: 1 case) and by 57% of PLGA (2+: 2 cases; 1+: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA. The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a high-grade tumor, with progression toward an entirely "inner cell" phenotype.
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PMID:C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. 1211 4

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.
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PMID:Increased expression of galectin-3 in primary gastric cancer and the metastatic lymph nodes. 1237 39

This study evaluated the expression of galectin-3 in 101 curettage specimens from normal, hyperplastic, and neoplastic endometrial tissues using immunohistochemistry. The histologic diagnoses were as follows: normal proliferative (n = 8) and secretory (n = 4) phase, simple hyperplasia (SH, n = 16), complex hyperplasia without atypia (CH, n = 11), atypical hyperplasia (AH, n = 13), endometrioid adenocarcinoma (EC, n = 35), serous papillary carcinoma (SPC, n = 10), and clear cell carcinoma (CC, n = 4). Immunostaining was scored with regard to the approximate percentage of positive tumor cells and relative staining intensity. The scores of immunostaining increased significantly from NE, SH, CH, and AH to the adenocarcinomas (ANOVA, p < 0.0001). Subsequently, three significantly different levels of galectin-3 expression were found (Newman-Keuls multiple comparison test). These consisted of (a) NE, SH, and CH, (b) AH and EC, and (c) SPC and CC. Galectin-3 expression increased with tumor grade (ANOVA, p = 0.0026). The scores of FIGO stages I to III did not differ significantly (ANOVA, p = 0.1687). Enhanced nuclear galectin-3 expression was noted in carcinomas, immunostaining of stromal cells decreased in the latter. This study shows that galectin-3 expression increases from normal and hyperplastic to atypical hyperplastic and cancerous states of endometrial tissues, and provides further evidence of a relationship between AH and EC.
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PMID:Galectin-3 expression in normal, hyperplastic, and neoplastic endometrial tissues. 1281 16

N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers have been shown to be efficient carriers for anticancer drugs because of their versatile chemistry and good biocompatibility. As demonstrated with hepatocytes, targeting efficacy of anticancer drugs could be further improved when the drug (doxorubicin) was conjugated to HPMA copolymers with biorecognisable groups, such as simple carbohydrates. The present study was devised to learn whether the cluster (multivalent) construction of carbohydrate residues could improve the targeting capability of HPMA copolymer-doxorubicin (DOX) conjugates towards human colon adenocarcinoma cells. DOX was linked via a lysosomally degradable tetrapeptide sequence to HPMA copolymers bearing galactosamine (GalN), lactose (Lac), or multivalent galactose residues (TriGal) to produce targetable polymeric drug carriers. The effect of the type of sugar moiety and its three-dimensional cluster arrangement on biorecognition by three human colon-adenocarcinoma cell lines was studied. The role of galectin-3 in the biorecognition of HPMA copolymer conjugates was explored. Biorecognition of the targetable (glycoside-bearing) conjugates decreased their IC(50) doses in comparison to the non-targetable (non-glycosylated) conjugates. The biorecognition of the TriGal-containing HPMA copolymer-doxorubicin conjugate by the cells was superior with concomitant decrease of its IC(50) doses. It is suggested that the increased cytotoxicity of the glycosylated HPMA-copolymer-DOX conjugates toward human colon-adenocarcinoma cells was caused by their biorecognition and effective internalisation via receptor-mediated endocytosis. All three human colon adenocarcinoma cell lines tested, Colo-205, SW-480 and SW-620, expressed the galectin-3 protein and the galectin-3-specific RNA. However, contrary to expectation, Colo-205 cells did not express a detectable amount of galectin-3 on the cell surface. This suggests that the binding of the glycoside-bearing HPMA copolymer-DOX conjugates to the cells was mediated not only by galectin-3. We conclude that targeting of the anticancer agent, doxorubicin, using HPMA copolymer conjugates bearing multivalent galactoside residues can improve their cytotoxicity.
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PMID:Design of a multivalent galactoside ligand for selective targeting of HPMA copolymer-doxorubicin conjugates to human colon cancer cells. 1468 99

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.
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PMID:Mucins and mucin binding proteins in colorectal cancer. 1500 Jan 51


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