Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis

Nakamori, Shoji; Kameyama, Masao; Imaoka, Shingi; Furukawa, Hiroshi; Ishikawa, Osamu; Sasaki, Yo; Izumi, Yuki; Irimura, Tatsuro

doi:10.1007/bf02258386

Cited by 124 publications

(87 citation statements)

References 33 publications

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“…The SLeX monoclonal antibodies could effectively restrain the adhesion of tumor cells to vascular endothelial cells and well reduce the formation of liver metastases of experimental nude mice. We speculate that the reason for the decrease of adhesion is that SLeX monoclonal antibodies may have sealed carbohydrate antigens on the tumor cell membrane site of SLex ligand and result in lower adhesive potential of tumor cells to vascular endothelial cells [27] . The results suggest that SLeX antigens play an important role in liver metastases of colon carcinoma.…”

Section: Discussionmentioning

confidence: 95%

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

Ding²,

Cai³

et al. 2001

WJG

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Section: Discussionmentioning

confidence: 95%

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

Ding²,

Cai³

et al. 2001

WJG

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“…There are significant correlations between the degree of expression of sialyl Lewis x/a determinants in cancer tissues and the postoperative prognosis of patients with colon, lung, breast, stomach, prostate, and urinary bladder cancers (10)(11)(12)(23)(24)(25)(26). Therefore, elimination of the sialyl Lewis x/a determinants from cancer cells has been an important goal for the control of cancer metastasis.…”

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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“…1, certain core structures, namely Tn, sTn, and T (core 1) antigens, are known to be associated with cancer. Core 2 is also important for the expression of sialyl Lewis x (sLe x ) epitope, a well known cancer-associated antigen (41)(42)(43). Core 2 formation leads to the extension of the core 2 branch on which the sLe x epitope frequently occurs in cancer cells (44,45).…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning and Characterization of a Novel UDP-GlcNAc:GalNAc-peptide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T6), an Enzyme Synthesizing the Core 3 Structure of O-Glycans

Iwai

Inaba

Naundorf

et al. 2002

Journal of Biological Chemistry

157

136

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The core 3 structure of the O-glycan, GlcNAc␤1-3Gal-NAc␣1-serine/threonine, an important precursor in the biosynthesis of mucin-type glycoproteins, is synthesized by UDP-N-acetylglucosamine:GalNAc-peptide ␤1,3-Nacetylglucosaminyltransferase (␤3Gn-T; core 3 synthase). The core 3 structure is restricted in its occurrence to mucins from specific tissues such as the stomach, small intestine, and colon. A partial sequence encoding a novel member of the human ␤3Gn-T family was found in one of the data bases. We cloned a complementary DNA of this gene and named it ␤3Gn-T6. The putative amino acid sequence of ␤3Gn-T6 retains the ␤3Gn-T motifs and is predicted to comprise a typical type II membrane protein. The soluble form of ␤3Gn-T6 expressed in insect cells showed ␤3Gn-T activity toward GalNAc␣-p-nitrophenyl and GalNAc␣1-serine/threonine. The ␤1,3-linkage between GlcNAc and GalNAc of the enzyme reaction product was confirmed by high performance liquid chromatography and NMR analyses. ␤3Gn-T6 effectively transferred a GlcNAc to the GalNAc residue on MUC1 mucin, resulting in the synthesis of a core 3 structure. Real time PCR analysis revealed that the ␤3Gn-T6 transcript was restricted in its distribution, mainly to the stomach, colon, and small intestine. We concluded that ␤3Gn-T6 is the most logical candidate for the core 3 synthase, which plays an important role in the synthesis of mucin-type O-glycans in digestive organs.

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Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis

Abstract: Increased expression of sLe(x) could be involved in establishment of colorectal cancer metastasis. It appears that examining sLe(x) expression may serve as a potent marker of the recurrence in patients with colorectal cancer.

Cited by 124 publications

References 33 publications

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

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

Molecular Cloning and Characterization of a Novel UDP-GlcNAc:GalNAc-peptide β1,3-N-Acetylglucosaminyltransferase (β3Gn-T6), an Enzyme Synthesizing the Core 3 Structure of O-Glycans

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