Anti-metastatic Effect of the Sialyl Lewis-X Analog GSC-150 on the Human Colon Carcinoma Derived Cell Line KM12-HX in the Mouse.

Shirota, Kenji; Kato, Yukio; Irimura, Tatsuro; Kondo, Hirosato; Sugiyama, Yuichi

doi:10.1248/bpb.24.316

Cited by 19 publications

(13 citation statements)

References 16 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Shirota and colleagues investigated the inhibitory effect of a sLe x analog, GSC-150 on hepatic metastasis of human colon carcinoma in nude mice. They found that liver metastases were significantly attenuated when cancer cells were co-administered with GSC-150 (Shirota et al, 2001). In addition to sLe x analogs, novel disaccharides have been generated which function as competitive substrate inhibitors for glycotransferases involved in the synthesis of sLe x .…”

Section: The Biology Of Selectin-mediated Hematogenous Metastasismentioning

confidence: 99%

Adhesion receptors as therapeutic targets for circulating tumor cells

Li¹,

King²

2012

Front. Oncol.

View full text Add to dashboard Cite

Metastasis contributes to >90% of cancer-associated mortality. Though primary tumors can be removed by surgical resection or chemo/radiotherapy, metastatic disease is a great challenge to treatment due to its systemic nature. As metastatic “seeds,” circulating tumor cells (CTCs) are believed to be responsible for dissemination from a primary tumor to anatomically distant organs. Despite the possibility of physical trapping of CTCs in microvessels, recent advances have provided insights into the involvement of a variety of adhesion molecules on CTCs. Such adhesion molecules facilitate direct interaction with the endothelium in specific tissues or indirectly through leukocytes. Importantly, significant progress has been made in understanding how these receptors confer enhanced invasion and survival advantage during hematogenous circulation of CTCs through recruitment of macrophages, neutrophils, platelets, and other cells. This review highlights the identification of novel adhesion molecules and how blocking their function can compromise successful seeding and colonization of CTCs in new microenvironment. Encouraged by existing diagnostic tools to identify and isolate CTCs, strategic targeting of these adhesion molecules to deliver conventional chemotherapeutics or novel apoptotic signals is discussed for the neutralization of CTCs in the circulation.

show abstract

Section: The Biology Of Selectin-mediated Hematogenous Metastasismentioning

confidence: 99%

Adhesion receptors as therapeutic targets for circulating tumor cells

Li¹,

King²

2012

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Shirota and coworkers developed GSC-150, a sLe X analog, and showed suppression of inflammation and reduced liver metastasis when administered to mice (Shirota et al, 2001) (Figure 6). Ulbrich and coworkers described dibenzoic acid-based pan-selectin inhibitors that block rolling and E-selectin adhesion in an induced peritonitis model of acute inflammation in mice (Table 6) (Ulbrich et al, 2006).…”

Section: Applications For O-linked Glycan Inhibitorsmentioning

confidence: 99%

Glycan Antagonists and Inhibitors: A Fount for Drug Discovery

Brown¹,

Crawford²

2007

Critical Reviews in Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Glycans, the carbohydrate chains of glycoproteins, proteoglycans, and glycolipids, represent a relatively unexploited area for drug development compared with other macromolecules. This review describes the major classes of glycans synthesized by animal cells, their mode of assembly, and available inhibitors for blocking their biosynthesis and function. Many of these agents have proven useful for studying the biological activities of glycans in isolated cells, during embryological development, and in physiology. Some are being used to develop drugs for treating metabolic disorders, cancer, and infection, suggesting that glycans are excellent targets for future drug development.

show abstract

“…The glycosylation pattern of tumor cells is therefore the focus in the development not only of new tools for tumor diagnosis and monitoring but also in the design of new anticancer drugs [8]. Attempts have been made to mount an immune response against tumor oligosaccharides by carbohydrate vaccines [9] and also to inhibit adhesive processes, such as the interaction between oligosaccharides and lectins, by synthetic carbohydrate analogues [10–13]. …”

Section: Introductionmentioning

confidence: 99%

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

Marano

Gronewold²,

Frank³

et al. 2012

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

SummaryOligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis.The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin.In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site.These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis(hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo.

show abstract

Anti-metastatic Effect of the Sialyl Lewis-X Analog GSC-150 on the Human Colon Carcinoma Derived Cell Line KM12-HX in the Mouse.

Cited by 19 publications

References 16 publications

Adhesion receptors as therapeutic targets for circulating tumor cells

Adhesion receptors as therapeutic targets for circulating tumor cells

Glycan Antagonists and Inhibitors: A Fount for Drug Discovery

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

Contact Info

Product

Resources

About