Recognition by Elam-1 of the Sialyl-Le
            <sup>x</sup>
            Determinant on Myeloid and Tumor Cells

Walz, Gerd; Aruffo, Alejandro; Kolanus, Waldemar; Bevilacqua, Michael P.; Seed, Brian

doi:10.1126/science.1701275

Cited by 926 publications

(384 citation statements)

References 41 publications

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“…Because both sialyl Lewis x and sialyl Lewis a on the cancer cell surface are ligands for E-selectin (13,14), we next examined the effects of directed expression of Sd a -h1,4GalNAcT on adhesion to endothelial cells. Whereas mock-transfected KATO III cells strongly adhered to activated HUVEC, the Sd a -h1,4GalNAcT-transfected KATO III cells showed significantly reduced adhesion ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Statistically significant correlations between the postoperative prognosis of the patients and the degree of expression of the sialyl Lewis x/a determinants in cancer tissues have been shown for both colon and stomach cancers (9)(10)(11)(12). Further, sialyl Lewis x and sialyl Lewis a determinants in cancer cells serve as ligands for E-selectin, which is inducibly expressed by endothelial cells and functions as a cell adhesion molecule (13,14). Thus, interactions between E-selectin and its specific carbohydrate ligands play a significant role in hematogenous metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Kawamura¹,

Kawashima²,

Fukunaga³

et al. 2005

Cancer Research

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The Sd a blood group carbohydrate structure is expressed in the normal gastrointestinal mucosa. We reported previously that the expression of Sd a carbohydrate structures and B1,4-N-acetylgalactosaminyltransferase (B1,4GalNAcT) activity responsible for Sd a synthesis were remarkably decreased in cancer lesions of the gastrointestinal tract. In this study, we found that Sd a antigen was expressed mainly in chief cells of normal stomach but not in cancer tissue by immunohistologic staining. In separated gastric mucosal cells, the Sd a glycolipids and B1,4GalNAcT activity were concentrated in a fraction that contained chief cells as a major population. We cloned the cDNA encoding the glycosyltransferase that catalyzes the synthesis of Sd a (Sd a -B1,4GalNAcT). Introduction of this cloned cDNA into KATO III gastric or HT29 colonic cancer cell lines, which originally expressed the E-selectin ligands, sialyl Lewis x and sialyl Lewis a , resulted in a marked increase in cell-surface expression of Sd a along with the concomitant total loss of both sialyl Lewis x and sialyl Lewis a . Both KATO III and HT29 cells transfected with the Sd a -b1,4GalNAcT gene showed significantly decreased adhesion to activated human umbilical vein endothelial cells when compared with mock-transfected cells. Sd a determinants showed no direct binding to . These Sd a -B1,4GalNAcT-transfected cells showed strikingly reduced metastatic potential in vivo when compared with mock-transfected cells. In summary, forced expression of Sd a carbohydrate determinant caused remarkable elimination of carbohydrate ligands for selectin and reduced metastasis of human gastrointestinal tract cancer cells. (Cancer Res 2005; 65(14): 6220-27)

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Kawamura¹,

Kawashima²,

Fukunaga³

et al. 2005

Cancer Research

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“…[21][22][23] Round culture dishes (Becton Dickinson) were incubated with a spot of goatanti-IgG (Sigma, 10 mg/ml in 50 mM Tris, pH 9.5, 90 min, 201C …”

Section: Isolation Of Endothelial Cellsmentioning

confidence: 99%

Inhibition of monocyte/endothelial cell interactions and monocyte adhesion molecule expression by the immunosuppressant mycophenolate mofetil

2003

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Study design: In vitro study on the effects of mycophenolate mofetil (MMF) on isolated human monocytes and endothelial cells. Objectives: Haematogenous macrophages play an essential role in the development of secondary damage following spinal cord injury (SCI), and there is evidence that the use of immunosuppressants such as MMF can reduce monocyte invasion and neuronal damage. Setting: University Hospital for Orthopaedic Surgery, Frankfurt am Main, Germany. Methods: The effects of MMF on the adhesion of human monocytes to human umbilical vein endothelial cells (HUVEC), monocyte binding to immobilised E-selectin, and monocyte expression of intercellular adhesion molecule (ICAM)-1, sialyl Lewis X (sLeX) and major histocompatibility complex (MHC)-II were studied. The binding of monocytes to E-selectin was examined by using purified and immobilised E-selectin fusion protein. Adhesion molecule expression was investigated by flow cytometry. Results: The binding of monocytes to HUVEC was significantly reduced by 30.1% after treatment of monocytes with MMF (10 mg/ml), whereas the pretreatment of HUVEC with MMF did not result in significant changes in monocyte adhesion. MMF forcefully inhibited monocyte binding to immobilised E-selectin by 55.7%. Furthermore, MMF significantly inhibited the upregulation of ICAM-1-and MHC-II-expression on monocytes stimulated with either lipopolysaccharide or interferon-g, whereas the expression of sLeX was not impaired. Toxic effects were excluded by propidium-iodide staining and measurement of fluoresceindiacetate metabolism. Conclusion: MMF can downregulate important monocytic adhesion molecules and inhibits monocyte adhesion to endothelial cells, thus indicating that treatment with MMF could be beneficial after SCI. Sponsorship: This study was supported by the DFG (Ha 2721/1-3), the Paul und Ursula KleinStiftung and the Stiftung Friedrichsheim.

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“…It was reported that these carbohydrate antigens are ligands for selectin, an adhesion molecule expressed on the vascular endothelial cells (Lowe et al, 1990;Phillips et al, 1990;Walz et al, 1990;Takada et al, 1991). In vitro study showed that these carbohydrates were involved in the adhesion of tumour cells from gastric carcinoma, colon carcinoma, hepatoma, pancreatic carcinoma and lung carcinoma to E-selectin, which is present on cytokine-activated human endothelial cells (Takada et al, 1993).…”

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confidence: 99%

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

et al. 2000

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SummarySialyl Lewis x antigen (SLX) is a carbohydrate antigen that serves as a ligand for selectin, an adhesion molecule expressed on vascular endothelial cells. The expression of SLX in 245 patients with advanced gastric carcinoma was examined immunohistochemically, and its clinicopathologic significance was analysed. We classified the patients with advanced gastric carcinoma into 91 with differentiated type and 154 with undifferentiated type. SLX expressed in 135 of 245 patients (55%), comprising 68 (75%) patients with differentiated carcinoma and 67 (44%) with undifferentiated carcinoma. The positive rate for SLX expression was significantly higher among patients with differentiated carcinoma than among those in undifferentiated carcinoma (P < 0.0001). With differentiated carcinoma, the incidence of lymph node metastasis, advanced tumour stage (stage III and IV) and liver recurrence was significantly higher in SLX-positive patients than in SLXnegative ones (P < 0.0001, P = 0.0065 and P = 0.028, respectively). Moreover, the prognoses were better in patients with SLX-negative tumours than in those with SLX-positive tumours (P = 0.019). With undifferentiated carcinoma, there were no significant correlations between SLX expression and any clinicopathological features or prognoses. The clinicopathologic significance of SLX expression in gastric carcinoma patients depends on histologic type. SLX expression may be of great relevance in predicting liver metastases in patients with differentiated carcinoma.

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Recognition by Elam-1 of the Sialyl-Le ^x Determinant on Myeloid and Tumor Cells

Cited by 926 publications

References 41 publications

Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Inhibition of monocyte/endothelial cell interactions and monocyte adhesion molecule expression by the immunosuppressant mycophenolate mofetil

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

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Recognition by Elam-1 of the Sialyl-Le x Determinant on Myeloid and Tumor Cells

Cited by 926 publications

References 41 publications

Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Introduction of Sda Carbohydrate Antigen in Gastrointestinal Cancer Cells Eliminates Selectin Ligands and Inhibits Metastasis

Inhibition of monocyte/endothelial cell interactions and monocyte adhesion molecule expression by the immunosuppressant mycophenolate mofetil

Clinicopathologic significance of sialyl Le xexpression in advanced gastric carcinoma

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Recognition by Elam-1 of the Sialyl-Le ^x Determinant on Myeloid and Tumor Cells