Increased tumorigenicity of rat colon carcinoma cells after ?1,2-fucosyltransferaseFTA anti-sense cDNA transfection

Hallouin, Florence; Goupille, Caroline; Bureau, Valérie; Méflah, Khaled; Pendu, Jacques Le

doi:10.1002/(sici)1097-0215(19990209)80:4<606::aid-ijc20>3.0.co;2-m

Cited by 22 publications

(12 citation statements)

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“…A similar alteration has been previously described in colon cell lines and human tumour tissues (14,20,21). similarly, strongly increased levels of the mrnA transcript for the α(1,2)Ft enzyme have also been observed in both human colorectal cancer and tumour cell lines (8,22), although the relative contribution of the two enzymes described for this classic activity, H and se, remains unclear.…”

Section: Discussionsupporting

confidence: 80%

α(1,2)fucosylation in human colorectal carcinoma

Muinelo-Romay

Gil‐Martín²,

Fernández-Briera³

2010

Oncology Letters

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Abstract. lewis b and lewis y (le) antigens are known to be elevated in colorectal tumours. Alterations in the catalytic behaviour of gDP-l-fucose:β-D-galactoside α(1,2) fucosyltransferase [α(1,2)Ft, ec: 2.4.1.69], the key enzyme in their synthesis, have been suggested as being responsible for these changes. In particular, an aberrant tumour-specific α(1,2)Ft activity that converts le a and le x to le b and le y determinants, respectively, has been reported in colorectal cancer tissues. to clarify the catalytic function of this enzyme during colorectal tumorigenesis, we analyzed α(1,2)Ft activity levels in healthy and tumour colon specimens using different acceptor substrates and determined the kinetic properties of the enzyme. to complete the study, the aberrant le a /le x α(1,2) fucosylation was determined in healthy and tumour colorectal tissues. A correlation analysis between the activity levels and various standard clinicopathological features, such as tumour stage, was also carried out to elucidate the role of these activities in tumour progression. The results obtained confirm the enhanced α(1,2)fucosylation in colorectal neoplastic tissues and the importance of the aberrant le a /le x α(1,2)Ft activity in this increase. However, taking into account the high levels of le a /le x fucosylation observed in healthy control tissues, we must rule out the idea of a colorectal tumour-specific α(1,2) FT. On the other hand, no significant association was observed between α(1,2)Ft activity levels and the clinicopathological characteristics. overall, our results suggest that α(1,2)Ft activity plays a critical role in the accumulation of le b and le y antigens in human colorectal carcinoma. IntroductionAlterations in glycosylation patterns are one of the characteristics associated with differentiation and malignant transformation (1). the oligosaccharide portions of cellular glycoconjugates, glycolipids and glycoproteins, convey specific immunodeterminants, such as the blood group and related antigens (2). these antigens are known to play an important role in cell recognition, interaction, adhesion and motility. Accordingly, changes in these antigens during carcinogenesis may be crucial in tumour progression and may be involved in extravasation and metastatic phenomena (3).ABo and related determinants are the result of the sequential addition of monosaccharide units to one of the five disaccharide precursors described. type 1 [galβ (1,3)glcnac β1-r] and 2 [gal β(1,4)glcnac β1-r] precursors produce H 1 and H 2 structures, respectively, after the addition of a fucose in α(1,2) linkage to the terminal β-galactosyl residue. H 1 and H 2 determinants can subsequently be converted into le b and le y difucosylated antigens by fucosylation in α(1,4) or α(1,3) linkage, respectively. their positional isomers, the le a and le x antigens, show a similar structure, but the antigens are not fucosylated in α(1,2) (4). Specific alterations of Lewis antigens have been reported in multiple carcinomas and have been correlated with the pr...

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Section: Discussionsupporting

confidence: 80%

α(1,2)fucosylation in human colorectal carcinoma

Muinelo-Romay

Gil‐Martín²,

Fernández-Briera³

2010

Oncology Letters

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“…We found a significant decrease in angiogenesis in Fut2 null mice compared to wt mice, suggesting the contribution of Fut2 in angiogenesis. Our data supports the notion that Fut2 and other fucosyltransferases play an important role in tumor growth and proliferation, a process in which angiogenesis is involved [5, 7, 30, 31]. …”

Section: Discussionsupporting

confidence: 89%

“…There are some disagreements regarding the role of Fut2 in tumor growth and angiogenesis. One group showed that transfection of a rat colorectal carcinoma cell line with rat Fut2 antisense ODNs decreased tumorigenicity [30, 31], while another study reported that development of colon tumors in mice is not affected in double Fut2 null and Smad3 null mice [32]. To clarify the contribution of Fut2 in angio-genesis, we employed Fut2 null ECs and Fut2 null mice in a number of angiogenesis assays.…”

Section: Discussionmentioning

confidence: 99%

A novel role for inducible Fut2 in angiogenesis

et al. 2012

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Rationale Angiogenesis plays an important role in wound healing and tumor growth. Fucosyltransferases synthesize fucosylated glycans and may play a major role in vascular biology. Objective To examine the role of an alpha(1,2) fucosyltransferase (Fut2) in angiogenesis. Methods and results We found that Fut2 mRNA and protein expression is inducible in human dermal micro-vascular endothelial cells (HMVECs). After finding that Fut2 is inducible in HMVECs, we examined if Fut2 contributes to angiogenesis. We found that Fut2 null endothelial cell (EC) migration and tube formation were significantly less compared to wild type (wt) ECs. Angio-genesis was impaired in Fut2 null compared to wt mice in the mouse Matrigel plug and the sponge granuloma angiogenesis assays. To assess the characteristics of Fut2 null ECs in vivo, we performed Matrigel plug angiogenesis assays in wt mice using Fut2 null and wt mouse ECs. We found a significant decrease in Fut2 null EC incorporation in neoangiogenesis compared to wt ECs. ERK1/2 activation, fibroblast growth factor receptor2, and vascular endothelial growth factor expression were less in Fut2 null ECs, suggesting a possible mechanism of impaired angio-genesis when Fut2 is lacking. Conclusions These data suggest a novel role for Fut2 as a regulator of angiogenesis.

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“…UEA‐1 stained the same band also in both FTA and FTB transfectants, but this antibody additionally stained a band at ≈ 100 kDa in the REG FTA transfectants. We showed previously that the high molecular mass band of ≈ 200 kDa detected by the three reagents in the REG FTB extracts corresponds to the product of a splice variant of CD44 carrying the product of exon v6 [28,29]. The lower molecular mass bands in the REG FTA extracts or the CHO cells glycoproteins, stained with either UEA‐I or MBr1, are not yet characterized.…”

Section: Resultsmentioning

confidence: 98%

Comparison of the three rat GDP‐L‐fucose:β‐D‐galactoside 2‐α‐L‐fucosyltransferases FTA, FTB and FTC

Bureau¹,

Marionneau²,

Cailleau-Thomas³

et al. 2001

European Journal of Biochemistry

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The complete coding sequences of three rat a1,2fucosyl-transferase genes were obtained. Sequence analysis revealed that these genes, called FTA, FTB and FTC, were homologous to human FUT1, FUT2 and Sec1, respectively. A distance analysis between all a1,2fucosyl-transferase sequences available showed that the two domains of the catalytic region evolved differently with little divergence between the FUT2 and Sec1 N-terminal domains, quite distant from that of FUT1. At variance, FUT1 and FUT2 C-terminal domains were less distant while a high evolutionary rate was noted for Sec1 C-terminal domain. Whereas FTA and FTB encode typical glycosyltransferases, FTC lacks the homologous start codon and encodes a protein devoid of intracellular and transmembrane domains. It is located on rat chromosome 1q34. Transfection experiments revealed that unlike FTA and FTB, FTC does not generate enzyme activity. Analysis by flow cytometry showed that H type 2 epitopes were synthesized in Chinese hamster ovary cells transfected by both FTA and FTB cDNA, but only FTB transfectants possessed H type 3 determinants. In REG rat carcinoma cells, both FTA and FTB allowed synthesis of H type 2 and H type 3 at the cell surface. Western blots showed that, in both cell types, FTA was able to synthesize H type 2 epitopes on a larger set of glycoproteins than FTB. Analysis of the kinetic parameters obtained using small oligosaccharides revealed only a slight preference of FTA for type 2 over other types of acceptor substrates, whereas FTB was barely able to fucosylate this substrate.

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Increased tumorigenicity of rat colon carcinoma cells after ?1,2-fucosyltransferaseFTA anti-sense cDNA transfection

Cited by 22 publications

References 15 publications

α(1,2)fucosylation in human colorectal carcinoma

α(1,2)fucosylation in human colorectal carcinoma

A novel role for inducible Fut2 in angiogenesis

Comparison of the three rat GDP‐L‐fucose:β‐D‐galactoside 2‐α‐L‐fucosyltransferases FTA, FTB and FTC

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