Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM)

Okada, Yoshio; Mugnai, Gabriele; Bremer, E.; Hakomori, Sen‐itiroh

doi:10.1016/0014-4827(84)90205-2

Cited by 85 publications

(57 citation statements)

References 21 publications

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“…(ii) Detergent-insolubility of GSLs together with pericellular matrix proteins and microfilaments at fibroblast adhesion sites, termed detergent-insoluble membrane (DIM) (9,10). (iii) Exclusive presence of ''fucolipids'' in villous membranes separated from intestinal mucosa (11), and enriched sphingolipids vs. glycerophospholipids in apical vs. basolateral membranes in kidney epithelial cells (12).…”

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confidence: 99%

The glycosynapse

Hakomori

2002

Proc. Natl. Acad. Sci. U.S.A.

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Physically distinguishable microdomains associated with various functional membrane proteins are one of the major current topics in cell biology. Glycosphingolipids present in such microdomains have been used as “markers;” however, the functional role of glycosyl epitopes in microdomains has received little attention. In this review, I have tried to summarize the evidence that glycosyl epitopes in microdomains mediate cell adhesion and signal transduction events that affect cellular phenotypes. Molecular assemblies that perform such functions are hereby termed “glycosynapse” in analogy to “immunological synapse,” the membrane assembly of immunocyte adhesion and signaling. Three types of glycosynapses are so far distinguishable: (i) Glycosphingolipids organized with cytoplasmic signal transducers and proteolipid tetraspanin with or without growth factor receptors; (ii) transmembrane mucin-type glycoproteins with clustered O-linked glycoepitopes for cell adhesion and associated signal transducers at lipid domain; and (iii) N-glycosylated transmembrane adhesion receptors complexed with tetraspanin and gangliosides, as typically seen with the integrin–tetraspanin–ganglioside complex. The possibility is discussed that glycosynapses give rise to a high degree of diversity and complexity of phenotypes

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confidence: 99%

The glycosynapse

Hakomori

2002

Proc. Natl. Acad. Sci. U.S.A.

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472

217

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“…S3). Glycolipids usually concentrate into lipid raft microdomains (21,30), in which glycolipid can reach high local concentrations and provide the multivalent attachment for C1q binding to the antibody-coated cell surface, which might also contribute to the effectiveness of glycolipids as antitumor targets (31).…”

Section: Discussionmentioning

confidence: 99%

Suppression of human prostate tumor growth by a unique prostate-specific monoclonal antibody F77 targeting a glycolipid marker

Zhang

Wang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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In our effort to find diagnostic markers and to develop therapeutic approaches for prostate cancer, we have identified an mAb that is capable of binding to a cell surface antigen specifically expressed on both androgen-dependent and androgen-independent prostate cancer cells. Immunohistological studies revealed that this mAb, called F77, stained 112 of 116 primary and 29 of 34 metastatic human prostate cancer specimens. Although the mAb F77 alone directly promotes prostate cancer cell death, it also mediates complementdependent cytotoxicity and antibody-dependent cellular cytotoxicity. In addition, mAb F77 can significantly inhibit androgenindependent PC3 and Du145 tumor growth in nude mice. Antigen characterization revealed that mAb F77 recognizes a very small molecular species with glycolipid properties. F77 antigen is concentrated in the lipid-raft microdomains, which serve as platforms for the assembly of associating protein complexes. Thus, the present study indicates that mAb F77 defines a unique prostate cancer marker and shows promising potential for diagnosis and treatment of prostate cancer, especially for androgen-independent metastatic prostate cancer.androgen-independent tumor | antibody therapy | prostate cancer lipid antigen (PCLA) | antibody-dependent cellular toxicity | lipid rafts P rostate cancer is the second leading cause of cancer-related death in men in the United States. Thirty percent to 45% of patients with clinically localized disease are found to have extracapsular extension (1), and cancer may relapse and metastasize after local therapy. Despite the effectiveness of hormone therapy, most patients with metastatic disease eventually progress to an androgen-independent state, at which time the disease is incurable. The 5-y survival rate for metastatic prostate cancer is only 34% (2). New therapeutic approaches are clearly needed for the treatment of advanced and metastatic prostate cancer.Targeted monoclonal antibody therapy has proven efficacious in clinical cancer treatment. Certain mAbs, such as the anti-CD20 mAb (rituximab) used to treat B cell lymphoma and the antip185Her2/neu mAb (trastuzumab) for metastatic breast cancer, have been reasonably efficacious on their own (3, 4). Our laboratory showed that mAbs to p185Her2/neu can reverse the malignant phenotype and render tumors more susceptible to concomitant genotoxic therapies (5).The antibodies currently available for detection and treatment of prostate cancers are limited. The mAb 7E11-C5.3, which binds to prostate-specific membrane antigen (PSMA), has been developed for clinical trials (6). The ProstaScint scan (Cytogen), based on 111

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“…Other experiments suggest that exogenously added sphingosine is also not enriched in the floating microdomain fraction. 2 The principal advantage of the HPLC technique employed in this study for measuring GSL levels is that it is very sensitive and allows clearer separation and identification of different GSL species when compared with thin layer chromatography. Unfortunately, glucosylceramide and sphingomyelin cannot be accurately quantified because of the specificity of ceramide glycanase.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

Vruchte

Lloyd-Evans

Veldman

et al. 2004

Journal of Biological Chemistry

168

138

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Glycosphingolipids are endocytosed and targeted to the Golgi apparatus but are mistargeted to lysosomes in sphingolipid storage disorders. Substrate reduction therapy utilizes imino sugars to inhibit glucosylceramide synthase and potentially abrogate the effects of storage. Niemann-Pick type C (NPC) disease is a disorder of intracellular transport where glycosphingolipids (GSLs) and cholesterol accumulate in endosomal compartments. The mechanisms of altered intracellular trafficking are not known but may involve the mistargeting and disrupted function of proteins associated with GSL membrane microdomains. Membrane microdomains were isolated by Triton X-100 and sucrose density gradient ultracentrifugation. High pressure liquid chromatography and mass spectrometric analysis of NPC1 ؊/؊ mouse brain revealed large increases in GSL. Sphingosine was also found to be a component of membrane microdomains, and in NPC liver and spleen, large increases in cholesterol and sphingosine were found. GSL and cholesterol levels were increased in mutant NPC1-null Chinese hamster ovary cells as well as U18666A and progesterone induced NPC cell culture models. However, inhibition of GSL synthesis in NPC cells with N-butyldeoxygalactonojirimycin led to marked decreases in GSL but only small decreases in cholesterol levels. Both annexin 2 and 6, membrane-associated proteins that are important in endocytic trafficking, show distorted distributions in NPC cells. Altered BODIPY lactosylceramide targeting, decreased endocytic uptake of a fluid phase marker, and mistargeting of annexin 2 (phenotypes associated with NPC) are reversed by inhibition of GSL synthesis. It is suggested that accumulating GSL is part of a mislocalized membrane microdomain and is responsible for the deficit in endocytic trafficking found in NPC disease.Increasing evidence suggests that the membranes of eukaryotic cells are not homogeneously fluid. They contain membrane microdomains, often referred to as lipid rafts and/or caveolae, enriched in glycosphingolipids (GSLs), 1 specific proteins, and cholesterol (1-3). Being operationally defined, i.e. by detergent insolubility and low buoyant density, the natural (in situ) existence of such membrane microdomains has been and continues to be controversial (4). However, they have recently been visualized by using electron microscopy as small structures covering as much as 35% of the cell surface (5). Although membrane microdomains on the cell surface tend to be transient (6), relatively stable microdomains have been visualized in the endocytic pathway (7) where they are proposed to play a role in protein and lipid sorting (8). Many GSL storage diseases, including Niemann-Pick type C (NPC), are often characterized by enlarged liver and spleen as well as severe neurodegeneration. In these diseases, cholesterol and GSLs accumulate in the endocytic pathway because of reduced breakdown. Hence, they may be a useful tool for determining the relative importance of GSLs in endocytic transport. Fibroblasts from patients suffering f...

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Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM)

Cited by 85 publications

References 21 publications

The glycosynapse

The glycosynapse

Suppression of human prostate tumor growth by a unique prostate-specific monoclonal antibody F77 targeting a glycolipid marker

Accumulation of Glycosphingolipids in Niemann-Pick C Disease Disrupts Endosomal Transport

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