Transgene Expression of α(1,2)-Fucosyltransferase-I (FUT1) in Tumor Cells Selectively Inhibits Sialyl-Lewis x Expression and Binding to E-Selectin without Affecting Synthesis of Sialyl-Lewis a or Binding to P-Selectin

Mathieu, Sylvie; Prorok, Maëlle; Benoliel, Anne‐Marie; Uch, Rathviro; Langlet, Claire; Bongrand, Pierre; Gerolami, René; El‐Battari, Assou

doi:10.1016/s0002-9440(10)63127-6

Cited by 53 publications

(51 citation statements)

References 41 publications

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“…While performing those experiments we had found that the hepatocarcinoma cells (HCC) HepG2, do not bind to P-selectin but interact with E-selectin exclusively through sLex glycoantigens. 11 We also found that HCC interact with L-selectin in a sulfate-dependent manner, but this interaction is not modified by FUT1 transduction. Thus, HepG2 cells represent a good model to study the role played solely by the inducible endothelial Eselectin and its tumoral partner sLex in the development of hepatocarinomas.…”

mentioning

confidence: 59%

“…The E-selectin-IgM chimera was produced by transiently transfecting the human 293-T cells as described. 11 …”

Section: Cell Lines Dnas and Lentiviral Transductionmentioning

confidence: 99%

“…The E-selectin binding was performed by incubating cell monolayers at 4°C for 30 min with the conditioned OptiMEM medium recovered from E-selectin-transfected 293T cells as described. 11 Bound E-selectin-IgM molecules were then stained with an Alexa Fluor 594-labeled anti-human IgM secondary antibody in OptiMEM/BSA. Cells were then visualised on a Zeiss Axiovert 200 fluorescence microscope with a 403 objective (Carl Zeiss, G€ ottingen, Germany).…”

Section: Antibodies Lectins and Fluorescence Analysesmentioning

confidence: 99%

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Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

Mathieu¹,

Gerolami²,

Luis³

et al. 2007

Intl Journal of Cancer

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The glycoantigen sialyl-Lewis x (sLex) and its isomer sialy-Lewis a (sLea) are frequently associated with advanced states of cancer and metastasis. In a previous work, we have shown that hepatocarcinoma cells (HCC) HepG2 interact with the endothelial Eselectin exclusively through sLe x oligosaccharides, the synthesis of which could be completely prevented by the a(1,2)-fucosyltransferase-I (FUT1), thus resulting in a strong inhibition of adhesion and rolling on activated endothelial cells. The purpose of the present study was to evaluate the impact of inhibiting sLex synthesis and the subsequent E-selectin adhesion, on HCC tumor growth in nude mice. Four weeks after subcutaneous transplantation of cells, no FUT1-derived tumor could be detected, whereas 75% of control animals developed large size tumor nodules. Between the 4th and the 8th week postinoculation, 33% tumors arose from FUT1-transduced cells but showed a slow growth (nodule volumes less than 500 mm 3 ), while more than 50% of control tumors reached volumes between 1,500 and 3,000 mm 3 . Several parameters were examined, including cell division and proliferation, apoptosis, adhesion to extracellular matrix components and angiogenesis/vasculogenesis. We provide evidence that among all, vasculogenesis was the most clearly affected by FUT1 expression, suggesting that tumor angiomorphogenesis may, at least partly, depend on Eselectin-mediated interaction between HCC and endothelial cells, the inhibition of which remarkably retards tumor growth. ' 2007 Wiley-Liss, Inc.Key words: a(1,2)-fucosyltransferase-I; E-selectin; sialyl-Lewis; antitumor; vasculogenesisThe sialyl-Lewis antigens (sLex and sLea) are blood grouprelated antigens naturally expressed on leukocytes to initiate leukocyte-endothelium interaction mediated by the cytokine-inducible endothelial adhesion molecule E-selectin. 1,2 In addition to this physiological role in inflammation, sialyl-Lewis antigens are also considered as tumor markers expressed on many cancer cells and therefore, they are thought to be involved in metastasis by initiating tumor cell-endothelium adhesion. 3 Indeed, the expression of sialyl-Lewis antigens on carcinoma cells is frequently associated with advanced states of cancer and a statistically relevant relationship has been established between the postoperative prognosis of patients and the degree of expression of sialyl-Lewis antigens on cancer tissues. 3 Besides, several lines of evidence from selectin-deficient mice studies pointed out the contribution of selectins in facilitating tumor growth and progression. 4,5 In particular, E-selectin and its sLex-containing glycoconjugate ligands have been shown to be involved in the essential events of tumor angiogenesis, 6-9 including the fact that coinjection of tumor cells expressing high level of sLe x together with endothelial cells constitutively expressing E-selectin, has been found to promote tumor angiogenesis and growth. 10 We have recently succeeded in strongly blocking the expression of sLex on digestive cancer cells...

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confidence: 59%

“…The E-selectin-IgM chimera was produced by transiently transfecting the human 293-T cells as described. 11 …”

Section: Cell Lines Dnas and Lentiviral Transductionmentioning

confidence: 99%

Section: Antibodies Lectins and Fluorescence Analysesmentioning

confidence: 99%

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Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

Mathieu¹,

Gerolami²,

Luis³

et al. 2007

Intl Journal of Cancer

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“…This characteristic substrate usage resulted in total elimination of sialyl Lewis x/a from both glycolipids and glycoproteins. Previously, two research groups introduced FUT1, which catalyzes the addition of a terminal fucose in a1,2 linkage to a lactosamine residue, into HT29 cancer cells and succeeded in reducing the level of sialyl Lewis x (32,33). However, their results with sialyl Lewis a were inconsistent.…”

Section: Discussionmentioning

confidence: 99%

“…However, their results with sialyl Lewis a were inconsistent. The discrepancy between these two studies seems to be derived from the heterogeneity of expression patterns of carbohydrates that can occur in a cancer cell line (33). This again indicates the difficulty in applying gene delivery of FUT1 for the treatment of cancer cells in the human gastrointestinal tract, which displays immense heterogeneity and variation.…”

Section: Discussionmentioning

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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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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Directing Flux in Glycan Biosynthetic Pathways with a Small Molecule Switch

Kohler¹,

Czlapinski²,

Laughlin³

et al. 2004

ChemBioChem

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Transgene Expression of α(1,2)-Fucosyltransferase-I (FUT1) in Tumor Cells Selectively Inhibits Sialyl-Lewis x Expression and Binding to E-Selectin without Affecting Synthesis of Sialyl-Lewis a or Binding to P-Selectin

Cited by 53 publications

References 41 publications

Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

Introducing α(1,2)‐linked fucose into hepatocarcinoma cells inhibits vasculogenesis and tumor growth

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

Directing Flux in Glycan Biosynthetic Pathways with a Small Molecule Switch

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