Expression of Blood Group Lewis b Determinant from Lewis a: Association of this Novel .alpha.(1,2)-L-Fucosylating Activity with the Lewis Type .alpha.(1,3/4)-L-Fucosyltransferase

Chandrasekaran, E. V.; Jain, Rakesh K.; Rhodes, J.; Srnka, Cheryl A.; Larsen, Robert D.; Matta, Khushi L.

doi:10.1021/bi00014a032

Cited by 25 publications

(11 citation statements)

References 15 publications

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“…the genetic origin of this 'aberrant' α(1,2)Ft is still unclear. Initially assumed to be a result of Se gene modulation during cancer transformation, it presently appears to be associated with the FUT3 gene that encodes the α(1,3/4)Ft lewis enzyme (25).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

α(1,2)fucosylation in human colorectal carcinoma

Muinelo-Romay

Gil‐Martín²,

Fernández-Briera³

2010

Oncology Letters

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“…The possibility that Le b biosynthesis in non-secretors takes place via A1,2 fucosylation of Le a has been proposed [23], and the authors suggested the existence of an, as yet unidentified, aberrant, A1,2FT in cancer cells [23]. A recent report proposed that such Le a acting activity is Fuc-TIII in COLO-205 cells [38]. Transfection experiments [24] and transgenic mice expressing Fuc-TIII [25] demonstrated that this enzyme promotes synthesis of both type 1 and 2 antigens (including SLe x).…”

Section: Discussionmentioning

confidence: 99%

β‐1,3‐galactosyltransferase and α‐1,2‐fucosyltransferase involved in the biosynthesis of type‐1‐chain carbohydrate antigens in human colon adenocarcinoma cell lines

Valli¹,

Gallanti²,

Bozzaro³

et al. 1998

European Journal of Biochemistry

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We studied the β-1,3-galactosyltransferase (GalT) and A-1,2-fucosyltansferase (FT) involved in the biosynthesis of type-1-chain carbohydrate antigens in human colon adenocarcinoma cell lines. We detected a GalT activity able to use GlcNAc as acceptor and found that lacto-N-biose I (Galβ1-3GlcNAc) is the only reaction product. Such β1,3GalT is kinetically similar to a pig trachea enzyme involved in mucin synthesis. The specific activity is high in cells that react strongly with anti-Lewis a and anti-Lewis b antibodies, and undetectable in a cell line that lacks antibody reaction. Reverse-transcriptase-mediated PCR analysis followed by DNA sequencing indicated that secretor-type A1,2FT is expressed in the cells, while the H type A1,2FT is not. The apparent K m values for donor and acceptor substrates determined for A1,2FT are similar to those of secretor-type A1,2FT and the specific activity measured correlates with Lewis b antigen expression on the cell surface. Moreover, some of the cell lines express Lewis y and H type 2 antigens, indicating that secretor type A1,2FT is responsible for their synthesis. Results suggest that biosynthesis of type-1-chain tumor-associated antigens in human colon carcinoma cells is operated by secretor-type A1,2FT, as reported in normal mucosa, and that β1,3GalT activity may play a relevant role in its control.Keywords : glycosyltransferase; carbohydrate antigen; colon carcinoma ; immunostaining.Association with tumor progression and malignancy has been reported for several carbohydrate antigens [1,2] and recent data suggest this is presumably due to their involvement in selectin-dependent tumor cell adhesion to the vascular endothelium [3,4]. Type-1-chain carbohydrate antigens such as SLe a (NeuAcA2-3Galβ1-3[FucA1-4]GlcNAc) and GlcNAc) are expressed in several cancers [1, 5Ϫ8]. Specific involvement of SLe a in selectin-dependent cell adhesion has been suggested [9, 10] and its stage-specific expression has been described in embryonic pancreas [11]. In the case of Le b, as well as in that of its type 2 chain counterpart Le y (FucA1-2Galβ1-4[FucA1-3]GlcNAc) [12,13], the molecular basis of their association with malignancy is still not fully elucidated.The biosynthesis of type-1-chain tumor markers depends on the activity of a galactosyltransferase (GalT) able to operate the Correspondence to

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“…However, Le b antigen levels in the plasma of the se2/se2 genotype were also high, and this results conflicts with the biosynthetic pathway. Another route by which the Le b antigen is biosynthesized from Le a antigen in colorectal carcinoma [29] and in gastric carcinoma and ovarium tumor [30] has been reported. This route might be related to the production of the Le b antigen in cord plasma (se2/se2).…”

Section: Discussionmentioning

confidence: 99%

Lewis and Secretor Gene Effects on Lewis Antigen and Postnatal Development of Lewis Blood Type

et al. 2001

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Lewis (Le) and Secretor (Se) gene effects on postnatal change in Lewis antigens are described based on the quantitative analysis of Lewis antigens in blood. Genuine Lewis blood types were determined by Le and Se genotyping in DNA samples obtained from umbilical cord blood and infant blood. Lewis^a (Le^a) and Lewis^b (Le^b) antigen levels were measured by a time-resolved fluoroimmunoassay. We found that Lewis phenotypes in infants over 9 months of age agreed with the genuine types. In cord blood, the dosage effect of the Se gene on antigen levels was observed, but the Le gene effect was not observed. Both Se and Le gene effects were observed in newborn babies’ blood 3–6 days after birth.

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Expression of Blood Group Lewis b Determinant from Lewis a: Association of this Novel .alpha.(1,2)-L-Fucosylating Activity with the Lewis Type .alpha.(1,3/4)-L-Fucosyltransferase

Cited by 25 publications

References 15 publications

α(1,2)fucosylation in human colorectal carcinoma

α(1,2)fucosylation in human colorectal carcinoma

β‐1,3‐galactosyltransferase and α‐1,2‐fucosyltransferase involved in the biosynthesis of type‐1‐chain carbohydrate antigens in human colon adenocarcinoma cell lines

Lewis and Secretor Gene Effects on Lewis Antigen and Postnatal Development of Lewis Blood Type

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