Disease relevance of LGALS1

• Knock-down of galectin-1 gene expression in melanoma cells promotes tumor rejection and stimulates the generation of a tumor-specific T cell-mediated response in syngeneic mice, showing that LGALS1 signaling in activated T-cells constitutes an important mechanism of tumor immune escape [1].
• Consistent with our previous results, we show that HIV-1 infection results in accumulation of exposed lactosamine residues, oligosaccharides recognized by galectin-1 on cell surface glycoproteins [2].
• This characterization was performed in BL36 cells, a Burkitt lymphoma cell line sensitive to GAL1 [3].
• This inhibition is specific to the Paramyxoviridae family because gal-1 did not inhibit fusion triggered by envelope glycoproteins of other viruses, including two retroviruses and a pox virus, but inhibited fusion triggered by envelope glycoproteins of the related Hendra virus and another paramyxovirus [4].
• Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines [4].
• Galectin-1 modulates human glioblastoma cell migration into the brain through modifications to the actin cytoskeleton and levels of expression of small GTPases [5].
• Subsequent analysis of several high-grade glioma cell lines demonstrated very high levels of galectin-1, regardless if the cell lines contained mutant or wild-type TP53 [6].
• Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1-expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells [7].

Psychiatry related information on LGALS1

• Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores [8].
• Depressive symptoms were assessed using the 18-item Human Population Laboratory Depression Scale (HPL) [9].

High impact information on LGALS1

• Estrogen induces the synthesis of a glycoprotein of molecular weight 46,000 daltons in three estrogen receptor-positive breast cancer cell lines (MCF7, ZR75 and T47D), but not in an estrogen receptor-negative cell line (BT 20) or a nonmalignant cell line (HBL 100) [10].
• Galectin-1-induced apoptosis required expression of CD45, and was decreased when N-glycan elongation was blocked by treatment of the cells by swainsonine, whereas inhibition of O-glycan elongation potentiated the apoptotic effect of galectin-1 [11].
• Apoptosis of T cells mediated by galectin-1 [11].
• Galectin-1 induced apoptosis of activated human T cells and human T leukaemia cell lines [11].
• We report here that galectin-1, expressed by stromal cells in human thymus and lymph nodes, is present at sites of cell death by apoptosis during normal T-cell development and maturation [11].

Chemical compound and disease context of LGALS1

• Forty proteins were identified, of which five [i.e., alpha-amylase; copper zinc superoxide dismutase; protein disulfide isomerase, pancreatic; tropomyosin 2 (TM2); and galectin-1] had been associated previously with pancreatic disease in gene expression studies [12].
• The cell density-dependent growth inhibition of human SK-N-MC neuroblastoma cells is initiated by increased ganglioside sialidase activity leading to elevated cell surface presentation of ganglioside GM1, a ligand of galectin-1 [13].
• In human HBL melanoma and HaCaT keratinocytes tumor necrosis factor alpha and H(2)O(2) both activated GPx in a time- and concentration-dependent manner (by 30-45 min). alpha-MSH peptides were found to inhibit the stimulated GPx activity and had biphasic dose-response curves [14].
• Fusion of HBL 100 cells, non-tumorigenic and characteristic of the basal cell lineage, with MCF-7 or MDA-MB-468 malignant breast cancer cells, characteristic of the luminal lineage, resulted in hybrid cells that displayed the phenotype of the HBL 100 cells [15].
• The human recombinant S-Lac lectin, L-14-II, produced in an Escherichia coli expression system, has been co-crystallized in the presence of lactose by the hanging drop vapor diffusion method [16].
• Anaplastic large cell lymphoma (ALCL), consistently expresses both Gal1 and its transcriptional regulator, c-Jun [17].

Biological context of LGALS1

• The genomic DNA encoding L-14-II (LGALS2) contains four exons with similar intron placement to L-14-I (LGALS1); but the genomic upstream region, which contains several sequences characteristic of regulatory elements, differs significantly from L-14-I [18].
• Two members of the S-lac lectin gene family, LGALS1 and LGALS2, reside in close proximity on human chromosome 22q12-q13 [19].
• Investigation of haplotype structure within the LGALS1 locus revealed five common haplotypes covering more than 95% of the test population [20].
• Resting T cells also bound galectin-1, but did not undergo apoptosis [11].
• Of importance for understanding the complex galectin network, it teaches the lesson that selection of cell surface ligands, route of signaling, and effects on regulators of cell cycle progression are markedly different between structurally closely related galectins [21].

Anatomical context of LGALS1

• We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface [22].
• Galectin-2 is structurally closely related to galectin-1, but has a distinct expression profile primarily confined to the gastrointestinal tract [21].
• Galectin-1 was strongly expressed on the endothelial cells of human kidney allografts, suggesting a role in the regulation of immune responses in transplantation [23].
• Reverse transcriptase-polymerase chain reaction analyses revealed that undifferentiated HL-60 cells expressed galectin-1, -3, -8, -9, and -10 (identical to Charcot Leyden crystal) mRNAs, and galectin-2, -4, and -7 were negligible before and after the differentiations [24].
• Galectin-1 is an endogenous human lectin that recognizes these types of glycosylation changes and induces cell death of activated lymphocytes [2].

Associations of LGALS1 with chemical compounds

• Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death [25].
• In contrast to galectin-1, the glycoproteins CD3 and CD7 are not ligands, while the shared affinity to beta1 integrin (or a closely associated glycoprotein) accounts for a substantial extent of cell surface binding [21].
• In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly [22].
• In a solid-phase binding assay, human recombinant galectin-1 bound immobilized human recombinant 90K in a fashion that was inhibitable by lactose [26].
• RESULTS: Gal-1 dramatically inhibited CY/G-CSF-induced HPC migration to the periphery as well as decreased peripheral neutrophilia and monocytosis in a dose- and time-dependent manner [27].
• The pseudopolyrotaxanes rapidly and efficiently precipitate Gal-1 and provide valency-corrected enhancements of up to 30-fold compared to native lactose and 20-fold over free LCD in a T-cell agglutination assay [28].

Physical interactions of LGALS1

• Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its apoptotic signal in T cell lines [29].
• We have found that galectin-1 binding to human T cell lines triggered rapid translocation of endonuclease G from mitochondria to nuclei [30].
• Moreover, galectin-1 binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T cell surface [31].
• Since anti-CBP70 was immunologically cross-reactive to np56, it is concluded that the galectin GCA binds to np56 via similar mechanisms as reported previously for the interaction of CBP-35 (galectin-3) and CBP-70 [32].
• We also found that galectin-3 interacted with Gemin4 and that it constituted one component of the complex co-immunoprecipitated with galectin-1 [33].

Regulatory relationships of LGALS1

• Preincubation of Jurkat E6.1 cells with cholera toxin or with the protein tyrosine kinase inhibitor herbimycin A reduced the gal-1 induced calcium response whereas the increase in [Ca(2+)](i)stimulated by CD2 or CD3 monoclonal antibodies (mAbs) was completely inhibited [34].
• Dimeric galectin-1 induces IL-10 production in T-lymphocytes: an important tool in the regulation of the immune response [23].
• Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death [30].
• This demonstrates a novel function for CD7 as a death trigger and identifies galectin-1/CD7 as a new biologic death signaling pair [35].
• Thus, CD43 bearing either core 1 or core 2 O-glycans can positively regulate T cell susceptibility to galectin-1, identifying a novel function for CD43 in controlling cell death [31].

Other interactions of LGALS1

• Involvement of CD2 and CD3 in galectin-1 induced signaling in human Jurkat T-cells [34].
• Moreover, the CD45 deficient Jurkat variant, J45.01 responds readily with tyrosine phosphorylation and subsequent apoptosis to galectin-1 treatment in a similar degree as its wild type counterpart, Jurkat does [29].
• In addition, CD7 that is required for galectin-1-induced death is not required for death triggered by galectin-3 [25].
• As an addition to the genetic information about LGALS2 reported earlier, we provide here a map of polymorphic sites within an 11-kb region containing the gene encoding a closely related molecule, galectin-1 (lectin, galactoside-binding, soluble, 1; LGALS1) [20].
• In this study, a marked increase in IL-10 mRNA and protein levels was demonstrated in non-activated and activated CD4(+) and CD8(+) T-cells, following treatment with a high concentration (dimeric form), but not a low concentration (monomeric form), of recombinant galectin-1 protein [23].
• Galectin-1 had no effect on phosphorylation of Smad3 at the linker region and C-terminus, whereas it decreased affinity of Smad3 to the SBE [36].

Analytical, diagnostic and therapeutic context of LGALS1

• These changes in galectin expressions were confirmed by Western blot and flow cytometry analyses [24].
• The results suggest that the ligation of CD2 and CD3 by gal-1 induces early events in T-cell activation comparable with that elicited by CD2 or CD3 mAbs [34].
• OBJECTIVE: The immunosuppressive and anti-inflammatory activity of mammalian galectin-1 (Gal-1) has been well established in experimental in vivo animal models and in vitro studies [27].
• Northern and Southern blot analyses indicate that the 14-kDa lectin is encoded for by a single gene [37].
• Molecular cloning, characterization, and expression of a human 14-kDa lectin [37].

References