Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Organ / tissue: capsuleAssociated disease: infection due to Escherichia coli [ICD11:
XN6P4 
]
NCBI PubMed ID: 17629853Publication DOI: 10.1055/s-2007-982087Journal NLM ID: 0431155Publisher: New York, NY: Thieme
Correspondence: klaus.elenius
utu.fi
Institutions: Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland, Pharmatest Services Ltd., Turku, Finland, BioTie Therapies Corp., Turku, Finland, Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel, Institute for Chemical and Biochemical Research ''G. Ronzoni'', Milan, Italy, Medicity Research Laboratory, and Department of Medical Biochemistry and Molecular Biology, University of Turku, and Department of Oncology, Turku University Hospital, Turku, Finland
Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. coli K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.
heparin, K5 polysaccharide, cancer, metastasis, anticoagulation
Structure type: polymer chemical repeating unit
Location inside paper: Fig.1, B, OS-K5PS
Compound class: O-polysaccharide, glucuronoglucan, sulfated polysaccharide
Contained glycoepitopes: IEDB_115136,IEDB_135813,IEDB_137340,IEDB_140630,IEDB_141807,IEDB_142354,IEDB_151531,IEDB_153764,IEDB_241119,IEDB_241120
Methods: deacetylation, acid hydrolysis, biological assays, reduction, cell growth, derivatization
Biological activity: OS-K5PS-HMW inhibited the metastasis of B16-BL6 cell to lungs in a concentration-dependent manner. OS-K5PS-HMW inhibited metastasis of breast cancer MDA-MB-231 cells to bone. Binding of B16-BL6 cells to ICAM-1 and P-selectin, but not to E-selectin, was diminished by treatment with OS-K5PS-HMW. OS-K5PS-HMW is largely devoid of anticoagulant activity.
Synthetic data: chemical
Related record ID(s): 45998, 46000
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GTC:G21552PE
Show glycosyltransferases
There is only one chemically distinct structure:
Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Organ / tissue: capsuleAssociated disease: infection due to Escherichia coli [ICD11:
XN6P4 ]
NCBI PubMed ID: 17629853Publication DOI: 10.1055/s-2007-982087Journal NLM ID: 0431155Publisher: New York, NY: Thieme
Correspondence: klaus.elenius
utu.fi
Institutions: Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland, Pharmatest Services Ltd., Turku, Finland, BioTie Therapies Corp., Turku, Finland, Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel, Institute for Chemical and Biochemical Research ''G. Ronzoni'', Milan, Italy, Medicity Research Laboratory, and Department of Medical Biochemistry and Molecular Biology, University of Turku, and Department of Oncology, Turku University Hospital, Turku, Finland
Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. coli K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.
heparin, K5 polysaccharide, cancer, metastasis, anticoagulation
Structure type: polymer chemical repeating unit
Location inside paper: Fig.1, C, NSOS-K5PS
Compound class: O-polysaccharide, glucuronoglucan, sulfated polysaccharide
Contained glycoepitopes: IEDB_115136,IEDB_137340,IEDB_140630,IEDB_141807,IEDB_151531,IEDB_241120,IEDB_241121
Methods: deacetylation, acid hydrolysis, biological assays, reduction, cell growth, derivatization
Biological activity: NSOS-K5PS-HMW inhibited the metastasis of B16-BL6 cell to lungs in a concentration-dependent manner
Synthetic data: chemical
Related record ID(s): 45998, 45999
NCBI Taxonomy refs (TaxIDs): 562Reference(s) to other database(s): GTC:G53884HR
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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