In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 14 ( 2005-07-15), p. 6220-6227
Abstract:
The Sda blood group carbohydrate structure is expressed in the normal gastrointestinal mucosa. We reported previously that the expression of Sda carbohydrate structures and β1,4-N-acetylgalactosaminyltransferase (β1,4GalNAcT) activity responsible for Sda synthesis were remarkably decreased in cancer lesions of the gastrointestinal tract. In this study, we found that Sda antigen was expressed mainly in chief cells of normal stomach but not in cancer tissue by immunohistologic staining. In separated gastric mucosal cells, the Sda glycolipids and β1,4GalNAcT 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 Sda (Sda-β1,4GalNAcT). Introduction of this cloned cDNA into KATO III gastric or HT29 colonic cancer cell lines, which originally expressed the E-selectin ligands, sialyl Lewisx and sialyl Lewisa, resulted in a marked increase in cell-surface expression of Sda along with the concomitant total loss of both sialyl Lewisx and sialyl Lewisa. Both KATO III and HT29 cells transfected with the Sda-β1,4GalNAcT gene showed significantly decreased adhesion to activated human umbilical vein endothelial cells when compared with mock-transfected cells. Sda determinants showed no direct binding to Siglec-3, -5, -7, and -9. These Sda-β1,4GalNAcT-transfected cells showed strikingly reduced metastatic potential in vivo when compared with mock-transfected cells. In summary, forced expression of Sda carbohydrate determinant caused remarkable elimination of carbohydrate ligands for selectin and reduced metastasis of human gastrointestinal tract cancer cells.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-05-0639
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2005
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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