Correlation between the sialylation of cell surface Thomsen-Friedenreich antigen and the metastatic potential of colon carcinoma cells in a mouse model.
The cell surface glycosylation profiles of a liver metastatic colon carcinoma variant cell line, SL4 cells previously selected from colon 38 cells in vivo for liver colonization were investigated. Flowcytometric analysis was performed with 7 plant lectins and 10 carbohydrate specific monoclonal antibodies. The results showed that peanut agglutinin (PNA), Sambucus nigra agglutinin, Ulex europeus agglutinin-I, anti-LeX, anti-LeY, and anti-Le(b) antibodies bound to the parental colon 38 cells but not to SL4 cells. Another variant cell line was selected in vitro for the paucity of cell surface PNA-binding sites using a magnetic cell sorter and was designated as 38-N4 cells. The binding profiles of plant lectins and carbohydrate-specific antibodies to 38-N4 cells were very similar to those of SL4 cells. After intrasplenic injections, metastatic ability of 38-N4 cells was higher than that of colon 38 cells. PNA binding to SL4 cells and 38-N4 cells was detected after sialidase treatment of these cells, indicating increased sialylation of Thomsen-Friedenreich antigen in these cells. The mRNA levels of sialyltransferases, ST3Gal I, ST3Gal II, ST6GalNAc I, and ST6GalNAc II, were compared. The level of ST3Gal II mRNA was elevated in both SL4 cells and 38-N4 cells, whereas the level of ST6GalNAc II mRNA was elevated in 38-N4 cells compared with colon 38 cells. According to the expression array analysis, there are other glycosyltransferase genes differentially expressed between SL4 and colon 38 cells, yet their involvement in the altered glycosylation in these cells is unclear.
Nemoto-Sasaki
Y
Y
Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Mitsuki
M
M
Morimoto-Tomita
M
M
Maeda
A
A
Tsuiji
M
M
Irimura
T
T
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D002240:Carbohydrate Sequence; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D018189:Immunomagnetic Separation / Q000379:methods; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009439:Neuraminidase / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D019887:Peanut Agglutinin / Q000378:metabolism; D011134:Polysaccharides / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013160:Splenic Neoplasms / Q000473:pathology / Q000556:secondary; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D015295:Antigens, Tumor-Associated, Carbohydrate; D019887:Peanut Agglutinin; D011134:Polysaccharides; D012333:RNA, Messenger; C016467:Thomsen-Friedenreich antigen; D012799:Sialyltransferases; D009439:Neuraminidase