Novel ganglioside found in adenocarcinoma cells of Lewis-negative patients.
We have precisely analyzed the structures of glycosphingolipids of human cancer cells and normal epithelial cells using several methods, including enzymatic release of carbohydrate moieties, fluorescent labeling, and identification using 2D mapping, enzymatic digestion, and mass spectrometry. These analyses enabled the identification of novel tumor-associated carbohydrate antigens that can be used to elucidate the involvement of carbohydrates in cancer malignancy and could act as candidate tumor markers. In our previous study, we identified a novel glycosphingolipid that accumulates in colon cancer cells, NeuAcα2-6(Fucα1-2)Galβ1-4GlcNAcβ1-3Galβ1-4Glc (α2-6 sialylated type 2H, ST2H). Here, structural analyses of cancer cells and normal epithelial cells from 60 colorectal and five pancreatic cancer patients, including four and two Lewis-negative individuals, respectively, reveal the presence of an additional novel glycosphingolipid, NeuAcα2-6(Fucα1-2)Galβ1-3GlcNAcβ1-3Galβ1-4Glc (α2-6 sialylated type 1H, ST1H). ST2H was found in colorectal and pancreatic cancer cells from about half of the cases. Unlike ST2H, ST1H was found in cancer cells from three out of six Lewis-negative patients (i.e., two cases of colorectal and one case of pancreatic cancer). However, the moiety was not found in normal epithelial cells or cancer cells from 59 Lewis-positive patients. These findings suggest that the accumulation of this carbohydrate antigen occurs predominantly in cancer cells of Lewis-negative patients. When the ST1H epitope is also carried on mucins as well as glycosphingolipids, this epitope is a promising tumor marker candidate, especially for Lewis-negative individuals.
Shida
Kyoko
K
Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Korekane
Hiroaki
H
Misonou
Yoshiko
Y
Noura
Shingo
S
Ohue
Masayuki
M
Takahashi
Hidenori
H
Ohigashi
Hiroaki
H
Ishikawa
Osamu
O
Miyamoto
Yasuhide
Y
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D002240:Carbohydrate Sequence; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000378:metabolism*
D014408:Biomarkers, Tumor; D005732:Gangliosides; D006028:Glycosphingolipids