P-selectin mediates metastatic progression through binding to sulfatides on tumor cells

Garcia, Josep; Callewaert, Nico; Borsig, Lubor

doi:10.1093/glycob/cwl059

Cited by 74 publications

(61 citation statements)

References 55 publications

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“…Nfil3 mediates IL-3 prosurvival functions in pro-B cells and its activation by dexamethasone correlates with down-regulation of proinflammatory mediators that are also down-regulated in tumor cells with constitutively active Stat3 (26). Selp (P-selectin) encodes an adhesion receptor expressed on platelets and endothelial cells and plays an important role in tumor metastasis (27,28). Finally Flt4, the receptor for Vegf-c, is important for tumor angiogenesis and lymphogenous metastasis (29,30).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Vallania

Schiavone

Dewilde

et al. 2009

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

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The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. However, the use of high throughput experimental methods, such as ChIP-chip and ChIP-sequencing, is limited by their high cost and strong dependence on cellular type and context. We developed a computational method for the genome-wide identification of functional transcription factor binding sites based on positional weight matrices, comparative genomics, and gene expression profiling. The method was applied to Stat3, a transcription factor playing crucial roles in inflammation, immunity and oncogenesis, and able to induce distinct subsets of target genes in different cell types or conditions. A newly generated positional weight matrix enabled us to assign affinity scores of high specificity, as measured by EMSA competition assays. Phylogenetic conservation with 7 vertebrate species was used to select the binding sites most likely to be functional. Validation was carried out on predicted sites within genes identified as differentially expressed in the presence or absence of Stat3 by microarray analysis. Twelve of the fourteen sites tested were bound by Stat3 in vivo, as assessed by Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional targets. Given its high validation rate, and the availability of large transcription factor-dependent gene expression datasets obtained under diverse experimental conditions, our approach appears to be a valid alternative to high-throughput experimental assays for the discovery of novel direct targets of transcription factors.chromatin immunoprecipitation ͉ phylogenetic footprint ͉ positional weight matrix ͉ Stat3 binding sites ͉ Stat3 target genes F unctional transcription factor binding sites (TFBSs) can be identified on a genomic scale either by computational approaches or through elaborated procedures such as chromatin immunoprecipitation followed by either genomic microchip hybridization (ChIP on Chip) or deep sequencing (ChIP and Sequencing) (1). These have the advantage of directly measuring the in vivo occupancy of genomic sites. By definition however, each experiment will only be able to identify sites bound under the specific conditions analyzed, i.e., separate experiments will have to be performed for each condition/tissue type of interest, and this will be particularly true for the many transcription factors (TF) that are known to induce distinct sets of genes in different tissues. Indeed, sets of TFBSs identified with these techniques in different conditions often show limited overlap. The predictions based on computational sequence analysis (2), however, are in principle independent of the cellular context. The ample collection of candidate BSs thus produced will then be available to identify transcriptional targets either as such or within lists of differentially expressed genes generated by microarray experiments, in many cases already available through public databases.The standard way to describe degenerate cis-regulator...

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Section: Discussionmentioning

confidence: 99%

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Vallania

Schiavone

Dewilde

et al. 2009

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

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“…Although sulfatide-mediated interactions of carcinomas with selectins were shown in vitro, their potential to facilitate metastasis has not been investigated. 3) Signaling pathways promoting migration and invasion include integrin and Akt. 24) Whether the sulfatides primarily inhibited integrin expression or subsequent downward signaling pathways simultaneously was not clarified in our study, but should be investigated in the future.…”

Section: Discussionmentioning

confidence: 99%

“…2) 3-Sulfatide on the surface of cancer cells possibly serves as a native ligand for selectin, possibly contributing to facilitation of metastasis. 3,4) Thus, it has been shown that 3-sulfatide mediated carcinoma adhesion to laminin and vitronectin, modulating metastatic potential. 5,6) Further, 3LL Lewis lung carcinoma cells that highly express sulfated lactosylcceramide exhibited low adhesiveness to fibronectin (FN) and laminin.…”

mentioning

confidence: 99%

Sulfatides Inhibit Adhesion, Migration, and Invasion of Murine Melanoma B16F10 Cell Line <i>in Vitro</i>

Ozawa

Sonoda

Kato

et al. 2012

Biological & Pharmaceutical Bulletin

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Endogenous sulfatide, such as 3-sulfated galactosylceramide (3-sulfatide) has been reported to be involved in neuronal development and regulation of tumor cell metastasis. Recently, a new 6-sulfated glucosylceramide (6-sulfatide) has been isolated from the ascidian, Ciona intestinalis. To determine the antitumor function of the new sulfatide, we examined the effects of synthetic 6-sulfatide and 3-sulfatide on the metastatic features of a murine melanoma cell line, B16F10. Both sulfatides significantly inhibited the adhesion of melanoma cells onto fibronectin-coated tissue plates and, the motility and invasion of the cells, with 6-sulfatide showing stronger inhibitory activities. In addition, both sulfatides inhibited α 5 -, and β 1 -but not α v -or β 3 -integrin expression. Furthermore, these sulfatides inhibited the activation of focal adhesion kinase, Akt, and extracellular signal-regulated kinase signaling pathways, which are thought to be important for cell migration and invasion. Therefore, these sulfatides may serve as promising drug candidates for the treatment of cancer metastasis.Key words sulfatide; adhesion; motility; invasion; melanoma 3-O-Sulfogalactosylceramide (3-sulfatide), was the first sulfolipid isolated from the human brain and other tissues. 3-Sulfatide has a variety of biological functions, on the nervous system, immune system, and bacterial infection.1) It interacts with several protein, including laminin, thrombospondin, antistatin, and human immunodeficiency virus type 1 gp120.2) 3-Sulfatide on the surface of cancer cells possibly serves as a native ligand for selectin, possibly contributing to facilitation of metastasis.3,4) Thus, it has been shown that 3-sulfatide mediated carcinoma adhesion to laminin and vitronectin, modulating metastatic potential. 5,6) Further, 3LL Lewis lung carcinoma cells that highly express sulfated lactosylcceramide exhibited low adhesiveness to fibronectin (FN) and laminin. These results are attributed to the decreased expression of α 5 -, α 6 -, and β 1 integrin. 7) On the other hand, exogenous 3-sulfatide can also bind to selectin and interfere the binding of selectin to neutrophils. 8,9) Metastasis of malignant tumor cells from the primary tumor to distant sites is a complex process including adhesion, migration, invasion, and proliferation. Adhesion of melanoma cells to blood vessels may be triggered by binding selectin and their ligand. These results raised the possibility that exogenous sulfatide can suppress the metastasis. Recently, a new type of 6-sulfated glucosylceramide (6-sulfatide) was isolated from the ascidian Ciona intestinalis, but its biological function remains unknown. This finding lead us to study the biological activity, particularly the effect on the metastatic function of 6-sulfatide. In this study, we synthesized two sulfatides, 3-sulfatide (1), as an endogenous sulfatide, and a new 6-O-(sodium oxysulfonyl)-β-D-glucopyranosyl-(1 1)-(2S,3S,4R)-2-hexadecanamido-octadecane-1,3,4-triol (6-sulfatide) (2) (Fig. 1A). We examined their effec...

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“…Metabolic inhibition of sulfation by incubation of mouse colon carcinoma MC-38 cells with sodium chlorate or enzymatic desulfation by treatment of the cells with arylsulfatase results in decreased P-selectin binding and leads to attenuation of metastasis in mouse lungs. Abundant sulfatide on the surfaces of cancer cells possibly serves as a native ligand for P-selectin, contributing to facilitation of metastasis ( 88,89 ) ( Table 4 ). The relationship between the initiation and promotion mechanism of cancer and elevated expression of sulfatide remains unknown.…”

Section: Hemostasis/thrombosismentioning

confidence: 99%

Role of sulfatide in normal and pathological cells and tissues

Takahashi

Suzuki

2012

Journal of Lipid Research

242

231

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P-selectin mediates metastatic progression through binding to sulfatides on tumor cells

Cited by 74 publications

References 55 publications

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3

Sulfatides Inhibit Adhesion, Migration, and Invasion of Murine Melanoma B16F10 Cell Line <i>in Vitro</i>

Role of sulfatide in normal and pathological cells and tissues

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