Glycomic mapping of pseudomucinous human ovarian cyst glycoproteins: identification of Lewis and sialyl Lewis glycotopes.
Expression of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) on cell-surface glycoproteins endows cells with the ability to adhere to E-, P-, and L-selectins present on endothelia, platelets, or leukocytes. Special arrangements of these glycotopes in cancers are thought to play a key role in metastasis. Previous studies have mostly described membrane-bound sLe(x) and sLe(a) activities. In this report, the major O-glycans of the secreted human ovarian cyst sialoglycoproteins from a Le(a+) nonsecretor individual (human ovarian cyst sample 350) were characterized by MS/MS analyses and immuno-/lectin-chemical assays. The results showed that HOC 350 carries a large number of epitopes for sLe(x), sLe(a), and Le(a) reactive antibodies. Advanced MS/MS sequencing coupled with mild periodate oxidation and exoglycosidase digestions further revealed that the O-glycans from HOC 350 are mostly of core 1 and 2 structures, extended and branched on the 3-arm with both type I and type II chains, complete with variable degrees of terminal sialylation and/or fucosylation to yield the sLe(x) or sLe(a) epitopes. Thus, the underlying core and peripheral backbone structures are similar to that of a previously proposed composite structural model for nonsialylated human ovarian cysts O-glycans, but with some notable distinguishing structural features in addition to sialylation.
Wu
Albert M
AM
Glyco-Immunochemistry Research Laboratory, Institute of Molecular and Cellular Biology, Chang-Gung University, Tao-yuan, Taiwan.
Khoo
Kay-Hooi
KH
Yu
Shin-Yi
SY
Yang
Zhangung
Z
Kannagi
Reiji
R
Watkins
Winifred M
WM
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D018395:CA-19-9 Antigen; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry; D005260:Female; D005732:Gangliosides / Q000032:analysis; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000032:analysis* / Q000737:chemistry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000032:analysis; D010048:Ovarian Cysts / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis* / Q000737:chemistry; D000080506:Sialyl Lewis X Antigen; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C410209:2-6 sialyl Le(a) antigen; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D000939:Epitopes; D005732:Gangliosides; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D011134:Polysaccharides; D012795:Sialoglycoproteins; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside