Disease relevance of Glycam1

• Characterization of the pathophysiologic roles of Lith3 and the new biliary mucin gene Glycam1 might provide insights into primary defects of human cholelithiasis and lead to new therapeutic strategies for prestone intervention [1].
• Toward a further characterization of L-selectin's carbohydrate specificity, we show that Sgp50 is partially inactivated by the linkage-specific Newcastle Disease virus sialidase (alpha 2,3 linkage) [2].
• EP2(-/-) mice exhibited significantly attenuated tumor growth and longer survival times when challenged with MC26 or Lewis lung carcinoma cell lines as compared with their wild-type littermates [3].
• RESULTS: Ibuprofen significantly inhibited cell proliferation in mouse (MC-26) and human (HT-29) colorectal cancer cell lines [4].
• In this study, the proliferative effects of retinoids were examined in the MC-26 and LoVo colon adenocarcinoma cell lines [5].

High impact information on Glycam1

• Sulphation requirement for GlyCAM-1, an endothelial ligand for L-selectin [6].
• The recently cloned Sgp50 (ref. 12), now designated GlyCAM-1, is a high endothelial venule-associated, mucin-like glycoprotein containing predominantly O-linked carbohydrate chains [6].
• We have used chlorate as a metabolic inhibitor of sulphation, and report here that GlyCAM-1 has an additional requirement for sulphate [6].
• Isolated CD34 and GlyCAM-1 from HEC-GlcNAc6ST-/- animals incorporate approximately 70% less sulfate than ligands from wild-type animals [7].
• The interaction of L-selectin expressed on lymphocytes with sulfated sialomucin ligands such as CD34 and GlyCAM-1 on high endothelial venules (HEV) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte recruitment [7].

Chemical compound and disease context of Glycam1

• To assess the antiproliferative effects of 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D3 in vitro, we cultured MC-26 (a colon cancer cell line) in the presence of 25(OH)D3 and 1,25(OH)2D3 and performed [3H]thymidine incorporation [8].
• METHODS: Hepatic metastases were induced by injecting 1 x 10(5) MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice [9].
• CsA had inhibitory effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine [10].
• In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and polyamine levels in MC-26 colon cancer in vitro [10].

Biological context of Glycam1

• These data suggest that this endothelial ligand is an adhesion molecule that accomplishes cell binding by presenting carbohydrate(s) to the lectin domain of L Selectin, and the name GLYCAM 1 (GLY-cosylation-dependent Cell Adhesion Molecule 1) has been proposed [11].
• The gene encoding GLYCAM 1 was found to map to murine chromosome 15 [11].
• It follows that soluble GlyCAM-1 may cross-link CD62L when it binds to cells, suggesting a mechanism for signal transduction [12].
• In CHO cells, PRL stimulated transcription of a luciferase reporter gene containing an 800-bp promoter fragment of GlyCAM 1, and progesterone partially suppressed the PRL effect [13].
• Here we examined GlyCAM-1 gene expression in mouse mammary epithelial cells [14].

Anatomical context of Glycam1

• GlyCAM-1 is a soluble secreted protein which, following binding to CD62L, stimulates beta2-integrin-mediated adhesion of lymphocytes [12].
• CD62L dissociates from GlyCAM-1 with a very fast dissociation rate constant (>/=10 s-1) which agrees well with the reported dissociation rate constant of CD62L-mediated leukocyte tethers [12].
• Overexpression of W37A and L83S mutants in primary mammary epithelial cells suppressed endogenous GlyCAM 1 expression [15].
• These data demonstrate that expression of GlyCAM 1 in mammary gland is under the control of both PRL and progesterone [13].
• GlyCAM 1 mRNA was highly induced by grafting pituitary glands from normal littermates [13].

Associations of Glycam1 with chemical compounds

• Similar to the in vivo studies, progesterone inhibited the induction of GlyCAM 1 transcription [13].
• In HC11 cells, GlyCAM 1 mRNA was induced in cells treated with insulin, dexamethasone, and PRL [13].
• From previous work, the binding of L-selectin to endothelial-associated glycoprotein ligands, GlyCAM-1 and CD34, requires oligosaccharide sialylation, sulfation, and probably fucosylation [16].
• We have recently identified a major capping group in GlyCAM-1 as 6' sulfated sialyl Lewis x, a novel structure which potentially satisfies all of these requirements [16].
• The majority of the O-glycans in GlyCAM-1 contain the T-antigen, i.e. Gal beta 1-->3GalNAc, which is incorporated into the core-2 structure, i.e. Gal beta 1-->3[GlcNAc beta 1-->6]GalNAc or larger core structures with additional GlcNAc residues [16].

Physical interactions of Glycam1

• At concentrations just above its mean serum level (approximately 1.5 microg/ml or approximately 30 nM), GlyCAM-1 binds multivalently to immobilized CD62L [12].

Regulatory relationships of Glycam1

• Progesterone inhibited both basal and PRL-stimulated GlyCAM 1 transcription [13].
• Two tandemly linked interferon-gamma-activated sequence elements in the promoter of glycosylation-dependent cell adhesion molecule 1 gene synergistically respond to prolactin in mouse mammary epithelial cells [15].
• LT-beta(-/-) HEVs expressed only abluminal PNAd and no HEC-6ST or GlyCAM-1 [17].

Other interactions of Glycam1

• The messenger RNA (mRNA) encoding GlyCAM 1 was present in mammary epithelia of PRL-stimulated mice [13].
• This review is focused on the immunological function of these molecules, especially glycosylation-dependent cell adhesion molecule-1 (GlyCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the mammary gland [18].
• In this study, analysis of LTbeta(-/-) mice identifies GlyCAM-1 as another LTbeta-dependent gene [19].
• LT-alpha(-/-) HEVs had no PNAd, HEC-6ST, or GlyCAM-1 [17].
• Analysis of draining auricular lymph node tissue sampled at 48 h following exposure to the potent contact allergen 2,4-dinitrofluorobenzene (DNFB) provided examples of up- and down-regulated genes, including onzin and guanylate binding protein 2, and glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1), respectively [20].

Analytical, diagnostic and therapeutic context of Glycam1

• Using surface plasmon resonance, we show that a soluble monomeric form of CD62L binds to purified immobilized GlyCAM-1 with a dissociation constant (Kd) of 108 microM [12].
• Trace amounts of mRNA for GlyCAM 1 were detected by RT-PCR in mammary tissue of PRL-/- mice [13].
• Immunohistochemistry indicated that GlyCAM 1 protein was detectable both in mammary epithelia and in the ductal lumen in PRL+/- virgin mice, but not in PRL-/- mice [13].
• GlyCAM-1 was metabolically labeled in lymph node organ culture with 35SO4 and a panel of tritiated carbohydrate precursors [21].
• To understand the functional role of secreted GlyCAM-1, we performed sandwich enzyme-linked immunosorbent assay to measure GlyCAM-1 plasma levels after inflammatory stimulus [22].

References