Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues

Ito, Hiroaki; Hiraiwa, Nozomu; Sawada‐Kasugai, Mikiko; Akamatsu, Suguru; Tachikawa, Tetsuya; Kasai, Yasushi; Akiyama, Seiji; Ito, Katuki; Takagi, Hiroshi; Kannagi, Reiji

doi:10.1002/(sici)1097-0215(19970516)71:4<556::aid-ijc9>3.0.co;2-t

Cited by 99 publications

(66 citation statements)

References 37 publications

(24 reference statements)

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“…adenocarcinomas and normal mucosa. [24][25][26] Although the down-regulation of expression of the Gal3ST-2 gene is evident as shown in Tables II, III, and Fig. 2, there exist substantial enzymatic activities in colonic non-mucinous adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Seko¹,

Nagata²,

Yonezawa³

et al. 2002

Japanese Journal of Cancer Research

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Expression levels of sulfomucin in human colonic adenocarcinomas are lower than those in normal colonic mucosa; this should be in part caused by down-regulation of expression of sulfotransferases, but it remains unclear which Gal 3-O-sulfotransferase (Gal3ST) is responsible for the biosynthesis of sulfomucin. In this study, we first examined the substrate specificities of four Gal3STs cloned so far, and found that Galβ β β β1 → → → →3GlcNAcβ β β β1 → → → → 3Galβ β β β1 → → → →4Glc (LNT) can be utilized only byGal3ST-2 as an acceptor substrate. The substrate specificity of Gal3ST-2 is closely similar to those of Gal3ST activities present in human normal mucosa and adenocarcinomas, suggesting that Gal3ST-2 is the dominant Gal3ST in colon and colonic cancer. Secondly, using LNT as a substrate, we comparatively analyzed levels of Gal3ST-2 activities in non-mucinous adenocarcinoma, mucinous adenocarcinomas, and the adjacent normal mucosa. We found that levels of Gal3ST-2 activities in non-mucinous adenocarcinoma are significantly lower than those in the adjacent normal mucosa, while those in mucinous adenocarcinomas are not significantly different from those in the adjacent normal mucosa. Moreover, we showed by a competitive RT-PCR method that expression levels of transcript for Gal3ST-2 in non-mucinous adenocarcinoma are lower than those in normal mucosa. These results suggest that Gal3ST-2 is one of the enzymes responsible for biosynthesis of sulfomucin, and that expression levels of Gal3ST-2 are down-regulated in non-mucinous adenocarcinoma.Key words: Colon cancer -Sulfomucin -Sulfotransferase -Gal3ST -Type 1Sulfomucin is a glycoprotein containing large amounts of O-linked, sulfated glycans. It is well-known that expression levels of sulfomucin in colonic cancer are markedly lower than those in the adjacent normal mucosa. 1, 2)Yamori et al.3) explored a monoclonal antibody, 91.9H, recognizing sulfated glycans in sulfomucin, and Irimura et al. 4) and Matsushita et al. 5) showed that expression levels of the epitope in colonic adenocarcinomas are indeed lower than those in normal mucosa. Thereafter, Loveless et al. 6) showed that the minimum epitope moiety is the SO 3 − →3Galβ1→3(Fucα1→4)GlcNAcβ1→3Galβ1→ structure. These results suggest that the decrease of the epitope in colon cancer is at least partly associated with that of sulfomucin. We previously showed that levels of the enzymatic activities of β1,3-galactosyltransferase, which can synthesize the backbone structure of the 91.9H antigen, are lower in colonic adenocarcinomas than in the adjacent normal mucosa. 7) Thereafter, Salvini et al. 8) showed that expression of β3GalT-V gene is down-regulated in colonic adenocarcinomas, suggesting that β3GalT-V gene is involved in biosynthesis of the 91.9H antigen and its low expression in colonic adenocarcinomas. However, it remains unclear whether or not 3-O-sulfation at the Gal residue is also down-regulated in the course of colonic carcinogenesis. Gal3ST transfers sulfate from PAPS to the C-3 position of Gal residu...

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Section: Discussionmentioning

confidence: 99%

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Seko¹,

Nagata²,

Yonezawa³

et al. 2002

Japanese Journal of Cancer Research

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“…9) However, cells of epithelial origin usually contain a significant amount of transcripts for other fucosyltransferase isoenzymes that are capable of synthesizing sialyl Lewis a/x ; i.e., mainly fucosyltransferases III and VI. The mRNA level of these major fucosyltransferase isoenzymes in epithelial cells shows no significant difference between colon cancer tissues and non-malignant colonic epithelial cells, 32,33) nor does the level explain the increased synthesis of sialyl Lewis x in cancer. Fucosyltransferase VII makes a substantial contribution to the synthesis in cells such as leukemic cells, which do not contain fucosyltransferase III or VI.…”

Section: Induction Of Sialyl Lewis A/x Expression In Epithelial Cancementioning

confidence: 92%

“…The role of selectin-mediated cell adhesion in cancer metastasis has mostly been considered in relation to patients with colon cancers, where hematogenous metastasis to the liver is the main factor determining the prognosis. [32][33][34][35][36] The increased expression of genes for some glycosyltransferases has been detected in colon cancer cells. Besides glycosyltransferases, expression of the genes for some sugar transporters such as GLUT-1 or UDP-galactose transporter was shown to be increased in cancers and implicated in the enhanced expression of sialyl Lewis a/x .…”

Section: Induction Of Sialyl Lewis A/x Expression In Epithelial Cancementioning

confidence: 99%

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

et al. 2004

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“…ST-30 PCR was performed as previously described 33 using the following primers: 5Ј-AGCGCAAGCTCTCGGCCT-3Ј (sense) and 5Ј-GTCACGT-TAGACTCAAAGTCT-3Ј (antisense). FucTIII PCR was performed as described 33 using the following primers: 5Ј-CTGCTG-GTGGCTGTGTGTTTCTTCTCCTAC-3Ј (sense) and 5Ј-CAG-CCAGCCGTAGGGCGTGAAGATGTCGGA-3Ј (antisense).…”

Section: Semiquantitative Rt-pcr Analysis For St-30 and Fuctiiimentioning

confidence: 99%

“…33 We assayed, therefore, if HNSCC variants differing in E48 expression, as well as in FX and sLe a expression, 21 would also differ in the expression of ST-30. FucTIII transfers fucose residues generated by the FX enzyme onto polylactosamine substrates, thus participating in the synthesis of fucosylated carbohydrate determinants such as sLe a .…”

Section: Expression Of St-30 and Fuctiii By Hnscc Variants Differing mentioning

confidence: 99%

Human Ly‐6 antigen E48 (Ly‐6D) regulates important interaction parameters between endothelial cells and head‐and‐neck squamous carcinoma cells

Eshel

Zanin

Kapon

et al. 2002

Intl Journal of Cancer

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Selectin ligands are crucial components in the interaction between endothelial cells and extravasating cancer cells and, thus, play an important role in metastasis formation. Headand-neck squamous cell carcinoma (HNSCC) variants expressing high levels of E48, a human Ly-6 protein (E48 hi ), expressed higher levels of the fucose-generating FX enzyme and of the fucosylated E-selectin ligand sLe a than cells expressing low levels of E48 (E48 lo ). Signaling through E48 upregulated expression levels of these molecules in HNSCC. Head-and-neck squamous cell carcinoma (HNSCC) is a major health problem. About 500,000 new cases are diagnosed annually worldwide. 1,2 Despite advances made in the diagnosis and treatment of HNSCC during the last decades, the treatment efficay and associated morbidity as well as the 5-year survival rate have only marginally improved. 3,4 However, the type of relapse is gradually shifting from locoregional recurrence to distant metastasis. 1 It is therefore critically important to develop novel treatment modalities. Advancement in the development of new forms of therapy depends to a large extent on the availability of additional information on and a profound understanding of the molecular and cellular mechanisms involved in HNSCC carcinogenesis and progression. There is already ample information on the genetic alterations in HNSCC, including mutation of p53, 5 amplification of PRAD-1 (chromosome 11q13) 6 and frequent LOH on 9p, 3p, 17p, 8p, 13q and 18q. 7 These alterations characterize specific histopathologic stages of HNSCC. However, the molecular mechanisms involved in lymphogenic and hematogenic metastasis formation remain unknown. These parameters obviously determine the prognosis of the disease.MAb E48 was 1 of several developed to detect and treat minimal residual HNSCC following primary treatment. 8 It recognizes an outer membrane antigen, expressed by HNSCC. This antigen was characterized by cDNA cloning 9 and proved to be a GPIanchored membrane protein expressed by squamous cells. E48 is highly (nearly 70%) homologous to the murine ThB protein, a member of the Ly-6 gene family. 9 -11 E48 maps on human chromosome 8q24, 9 the syntenic locus of mouse chromosome 15E, to which the mouse Ly-6 gene family has been mapped. 11 Whereas both E48 and ThB are expressed on keratinocytes of squamous epithelia, 9 they differ in lymphocyte expression. ThB is expressed by mouse lymphocytes, whereas E48 is not expressed by human lymphocytes. 12 The function of E48 on keratinocytes of squamous epithelia remains unclear, though it might be involved in cellular adhesion. 9 Shortly after the cloning of cDNA encoding the E48 antigen, several additional human Ly-6 genes were cloned. [13][14][15][16][17] Our laboratory reported previously on a linkage between the overexpression of certain Ly-6 proteins on mouse tumor cells and a high-malignancy phenotype of such cells. 18 -20 In view of the association of Ly-6 with a high-malignancy phenotype of mouse tumors, it was of interest to study the role, if any, pla...

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Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues

Cited by 99 publications

References 37 publications

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Down‐regulation of Gal 3–O‐sulfotransferase‐2 (Gal3ST‐2) Expression in Human Colonic Non‐mucinous Adenocarcinoma

Carbohydrate‐mediated cell adhesion in cancer metastasis and angiogenesis

Human Ly‐6 antigen E48 (Ly‐6D) regulates important interaction parameters between endothelial cells and head‐and‐neck squamous carcinoma cells

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