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)

Phenotypic and functional changes associated with tumor-bearing host (TBH) macrophages (M phi) are partly responsible for immunosuppression during tumor growth. Flow cytofluorometric analyses revealed differences in cell-cycle kinetics between normal host (NH) and TBH M phi that were stimulated at specific receptors. Receptor-ligand interactions were induced by antibodies against Mac-1, -2, -3, and Ia receptors and changes in DNA synthesis were measured over a 12-h time course by incorporation of propidium iodide. TBH M phi showed higher DNA synthesis than NH M phi over this time course irrespective of the receptor induced. NH M phi stimulated at the Mac-1 receptor demonstrated higher DNA synthesis than control NH M phi although TBH M phi stimulated at this receptor and control TBH M phi failed to show any differences. Both NH and TBH M phi exhibited small, short-term decreases in DNA synthesis when stimulated at the Mac-2 receptor. TBH M phi that were stimulated at the Mac-3 receptor demonstrated higher DNA synthesis than their control counterparts while NH M phi stimulated at this receptor and control NH M phi showed identical levels of DNA synthesis. No differences in DNA synthesis were found among normal or TBH M phi that were stimulated through Ia. Differences in DNA synthesis did not appear to be attributable to differences in receptor expression. Further analysis of Mac-1 and Mac-3 stimulated cells revealed that DNA synthesis in NH M phi stimulated at the Mac-1 receptor returned to control levels at 48 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macrophages stimulated by receptor-ligand interactions exhibit differences in cell-cycle kinetics during tumor growth: stimulation at Mac-1 and Mac-3 receptors alters DNA synthesis. 154 36

Heat-killed Lactobacillus casei YIT9018 (LC9018), when administered intravenously to normal mice, induced increase in Mac-1+ cells and Mac-2+ cells but not in Mac-3+ cells in spleen. The number of both populations changed in the same time course and was maximal 14 d after the administration. To know the effect of LC9018 on hematopoietic progenitor level, we examined the number of macrophage colony-forming cells (M-CFC), granulocyte-macrophage CFC (GM-CFC), and colony-forming units in spleen (CFU-S) in bone marrow 3 d after the administration. LC9018 stimulated the proliferation of M-CFC but not that of GM-CFC and CFU-S. LC9018-induced M-CFC were similar to normal M-CFC in dependence on macrophage colony-stimulating factor (M-CSF) and buoyant density. M-CFC-derived macrophages cultured in the presence of M-CSF expressed Mac-1 and Mac-2 but not Mac-3. They showed cytotoxic activity against syngenic tumor cells, Meth A, via direct contact, when assayed by using an in vitro colony inhibition assay or an in vivo Winn test. These results indicate that LC9018 stimulates the proliferation of cytotoxic macrophage progenitors in bone marrow and induces their differentiation in spleen. These effects may be one of the ways in which LC9018 suppresses tumor growth.
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PMID:Increased production of cytotoxic macrophage progenitors by Lactobacillus casei in mice. 250 42

Rat anti-mouse monoclonal antibodies (mAb), anti-Mac-1, -2, and -3, directed against macrophage (M phi) glycoprotein surface antigens, were used to demonstrate a tumor-induced shift in peritoneal M phi subpopulations. This study of the tumor-induced shift was approached in two steps. First, to show that separate phenotypic M phi subpopulations existed and second, to show that a shift in these populations was involved in immunosuppression of the host during tumor growth. Endogenous peroxidase activity was examined among normal and tumor-bearing host (TBH) M phi. A significant increase in the number of peroxidase-positive M phi occurred during tumor growth. Indirect immunofluorescence showed a decrease in Mac-2+ cells and an increase in Mac-3+ cells in TBH M phi populations. When the mAb, anti-Mac-1,-2, and -3 were used in the presence of complement (C), they were cytotoxic for M phi and showed differential depletion of normal and TBH M phi. Peroxidase-positive TBH M phi were susceptible to C-mediated lysis by anti-Mac-1 and -3 but not by anti-Mac-2, whereas no direct relationship was observed among normal host M phi. To demonstrate differences between normal and TBH M phi subpopulations, soluble inhibitory factors were examined from mAb plus C-modified M phi populations. Anti-Mac plus C-treated normal and TBH M phi produced supernatants with different regulatory capabilities as assessed in the mixed-lymphocyte reaction (MLR). Anti-Mac-2 plus C treatment significantly reduced the ability of TBH M phi to produce a soluble suppressor(s) but did not alter normal host M phi-derived suppressor production. In contrast, anti-Mac-1 and -3 plus C treatment of normal host M phi significantly reduced suppressor production. In the TBH, however, anti-Mac-1 plus C had no effect, while anti-Mac-3 plus C had only a limited reduction as compared to the normal host. Determination of levels of prostaglandin E2 (PGE2) in M phi supernatants showed that normal host Mac-1+ M phi were involved in down regulation of PGE2 production. This control was missing in the TBH M phi. Mac-2+ M phi were the apparent producers of PGE2 which accounts for the factor-mediated MLR suppression attributed to TBH Mac-2+ M phi. Collectively, these data suggest that tumor-induced aberrations in immunoregulation can in part be attributed to differences in anti-Mac mAb-defined M phi subpopulations.
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PMID:Shifts in macrophage (M phi) surface phenotypes during tumor growth: association of Mac-2+ and Mac-3+ M phi with immunosuppressive activity. 295 65

Three monoclonal antibodies, anti-Mac-1, -2, and -3, were used to modify accessory cell activity of whole spleen cell (WSC) or splenic adherent cell (SAC) preparations from normal or tumor-bearing hosts (TBH). Ligand activation by anti-Mac-1, -2 and -3 modified normal and TBH WSC lectin responses differentially; the most pronounced effect was with anti-Mac 1, which augmented normal WSC responsiveness, whereas anti-Mac-2 and -3 augmented TBH WSC mitogenesis. Ligand interaction with Mac-2 epitopes resulted in significantly suppressed normal host WSC responsiveness. With complement, anti-Mac-1 and -3 each reduced normal and TBH WSC proliferation. Reconstitution of blastogenesis was obtained by combining Mac-2-depleted with Mac-3-depleted normal host WSC or by combining Mac-1-depleted with Mac-2-depleted TBH WSC. To evaluate the role of different types of splenic adherent cells in T cell lectin responsiveness, adherent cells were collected and depleted by antibody plus complement treatment and added back to normal T cells. Removal of TBH SAC indicated the number of Mac-1+ SAC susceptible to lysis increased during tumor growth, whereas those susceptible to anti-Mac-2 and -3 treatment decreased. Removal of Mac-1+ normal host SAC stimulated the supportive accessory function of the remaining SAC. Enhancing accessory cell function diminished after removal of Mac-2+ or Mac-1+ normal and TBH SAC, respectively. T cell responsiveness was increased by adding back combinations of normal host SAC, Mac-1-depleted with Mac-3-depleted SAC or Mac-1-depleted with Mac-2-depleted SAC but not by Mac-2-depleted with Mac-3-depleted SAC. In contrast, none of the TBH SAC combinations were completely restored in accessory activity. In summary, SAC from normal host demonstrated an accessory cell function corresponding to a Mac-1- phenotype, which was either replaced or obscured by the predominance of a Mac-1+ phenotype in TBH.
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PMID:Changes in splenic macrophage Mac antigen expression during tumor growth: a kinetic study of accessory cell function and antigen-defined phenotypes. 353 82

The galactose-specific animal lectin, Mac-2, has been identified in macrophage (M phi) membrane, cytoplasmic, and nuclear fractions. Flow cytometric analyses showed that there is a decrease in membrane Mac-2 during tumor growth. After 24-h adherence there was an increase in the number of normal host (NH) and tumor-bearing host (TBH) Mac-2+ M phi. Immunoblot analyses of NH and TBH M phi identified changes in the subcellular localization of Mac-2. The increase in nuclear Mac-2 during tumor growth, and after prolonged adherence of NH and TBH M phi, correlates with an increase in M phi entering the late G1 phases of the cell cycle. Northern blot analyses showed an increase in Mac-2 mRNA during tumor growth, and an increase in NH and TBH M phi after 24-h adherence. Tumor growth is able to manipulate the immune system through M phi by causing a down-regulation in membrane Mac-2 and an up-regulation in intracellular Mac-2. NH and TBH M phi respond to adherence by expressing increased membrane and nuclear Mac-2, but TBH M phi response is lower.
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PMID:Tumor growth and adherence change the expression of macrophage Mac-2. 848 95

Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis. However, conflicting results on their function in the regulation of cell proliferation and differentiation during angiogenesis have been reported. We have examined the role of galectin-3 in the regulation of human umbilical vein endothelial cell proliferation, differentiation, migration, and neovascularization. Galectin-3, a carbohydrate-binding protein, with specificity for type 1 and 11 ABH blood group epitopes and polylactosamine glycan containing cell surface glycoproteins, is the major nonintegrin cellular laminin-binding protein. Because galectin-3 expression was shown to be associated in some tumor systems with metastasis, we questioned whether it induces endothelial cell morphogenesis. Here we show that galectin-3 affects chemotaxis and morphology and stimulates capillary tube formation of HUV-EC-C in vitro and angiogenesis in vivo. Endothelial cell morphogenesis is a carbohydrate-dependent process, as it is neutralized by specific sugars and antibodies. These findings demonstrate that endothelial cell surface carbohydrate recognition event(s) can induce a signaling cascade leading to the differentiation and angiogenesis of endothelial cells.
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PMID:Galectin-3 induces endothelial cell morphogenesis and angiogenesis. 1070 7

Galectin-3 is an endogenous beta-galactoside-binding protein with specificity for type I and II ABH blood group epitopes and poly-N-acetyllactosamine glycan-containing cell surface glycoproteins and is the major nonintegrin cellular laminin-binding protein. Galectin-3 is expressed at an elevated level in a wide range of neoplasms, and expression was shown to be associated in some tumor cell systems with metastases. Here we determined the functional consequence of blocking galectin-3 expression in highly malignant human breast carcinoma MDA-MB-435 cells. Inhibition of galectin-3 expression led to reversion of the transformed phenotype as determined by altered morphology, loss of serum-independent growth, acquisition of growth inhibition properties by cell contact, and abrogation of anchorage-independent growth. The blockage of galectin-3 expression led to a significant suppression of tumor growth in nude mice. These results provide direct evidence that galectin-3 expression is necessary for the maintenance of the transformed and tumorigenic phenotype of MDA-MB-435 breast carcinoma cells.
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PMID:Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells. 1129 62

Galectin-3 belongs to a group of endogenous lectins with an affinity to glycoconjugates containing beta-galactoside residues. It has been detected in numerous tissues and studied in connection with tumor growth, dedifferentiation, and metastasis. Only few studies have dealt with galectin-3 detection in tumors of the thyroid gland and with its possible role for differential diagnosis. We studied 118 cases of thyroid gland tumors with a monoclonal antibody against galectin-3; we compared the preparations by a semiquantitative score to determine differences in expression. Normal thyroid gland tissue, goiter tissue, and tissue with functional enhancement were largely negative for galectin-3. Adenomas with a typical cytological pattern were predominantly negative, but a focal positive reaction in single cells and cell groups or follicles was possible. Almost all papillary carcinomas showed a distinct galectin-3 expression. While findings in follicular carcinomas and oxyphilic adenomas and carcinomas were very uneven, with both positive and negative tumors, the galectin-3 reaction can be helpful in recognizing follicular variants of the papillary carcinoma. Investigation of the biological significance of tumors should always be cautious and consider known histological criteria for malignancy.
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PMID:[Expression of galectin-3 in thyroid gland and follicular cell tumors of the thyroid. A critical study of its possible role in preoperative differential diagnosis]. 1140 51

Osteopontin (OPN) expression in tumors is associated with more aggressive tumor growth; however, several studies have suggested that OPN as a host protein can regulate tumor growth as well. OPN is produced by macrophages and T cells, and reportedly modifies macrophage function. Here, we have investigated the effect of OPN on macrophage function, and its role in host defense against tumor growth. OPN deficient (-/-) and wild-type (WT) peritoneal macrophages were assessed for their ability to mediate cytotoxicity of tumor cells. Thioglycollate-elicited peritoneal exudate cells (PEC) were stimulated in vitro with interferon-gamma and lipopolysaccharide. [(3)H]Thymidine-labeled ras-transformed tumor cells were then added and (3)H release and nitrite accumulation were measured. OPN -/- PEC exhibited as much as a 70% reduction in cytotoxicity as compared to WT PEC. Tumor cell OPN status, on the other hand, had little effect on the extent of cytotoxicity. Production of nitrite by the PEC correlated with their capacity to kill tumor cells. L-929 cells, which are relatively resistant to nitric oxide-induced cytotoxicity and sensitive to that effected by TNF-alpha, were killed equally well by wild-type and OPN-deficient PEC, suggesting that the effect of OPN is not mediated through TNF-alpha. No difference was seen in the cytotoxicity of resident macrophages from mice of different genotypes, indicating that the defect in the OPN-deficient macrophages may result from altered differentiation in vivo. In support of this idea, we show that the expression of the macrophage markers F4/80 in peritoneal cells and of Mac-2 in spleen cells is altered in OPN -/- mice as compared to WT. These data support the hypothesis that host-derived osteopontin may inhibit tumor growth and provide a mechanism for this effect.
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PMID:Impaired anti-tumor cytotoxicity of macrophages from osteopontin-deficient mice. 1505 10

Galectin-3, a multifunctional lectin, is involved during cancer progression. Previous observations showed that both cytosolic expression and nuclear exclusion of galectin-3 in human prostate cancer cells were associated to progression of the disease. In this study, we examined the biological roles of galectin-3 when expressed either in the nucleus or in the cytosol. LNCaP, a galectin-3-negative human prostate cancer cell line, was used to generate transfectants expressing galectin-3 either in the nucleus or in the cytosol. No changes in cell morphology, proliferation, attachment to laminin-1 or androgen dependency were observed. Cytoplasmic galectin-3 induced significantly increased Matrigel invasion, anchorage-independent growth and in vivo tumor growth and angiogenesis, and decreased inducible apoptosis. Surprisingly, nuclear galectin-3 affected these parameters in an opposite fashion with an overall antitumoral activity. Thus, our study demonstrates that galectin-3 exerts opposite biological activities according to its cellular localization: nuclear galectin-3 plays antitumor functions and cytoplasmic galectin-3 promotes tumor progression.
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PMID:Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3. 1532 83


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