Sialylated core 1 based O-linked glycans enhance the growth rate of mammary carcinoma cells in MUC1 transgenic mice.
The MUC1 mucin, found on the luminal surface of simple epithelial cells is upregulated and aberrantly glycosylated in many carcinomas particularly breast and ovarian. MUC1 expressed by normal mammary epithelial cells, carries core 2 glycans but in breast carcinomas the simple core 1 based glycans are added. The binding of the monoclonal antibody SM3 to its peptide epitope in the tandem repeat of MUC1 is blocked by the branched core 2 glycans found on MUC1 expressed by normal cells. Thus SM3 does not bind to MUC1 expressed by normal mammary epithelial cells but reacts with more than 90% of breast carcinomas, suggesting that the loss of at least some core 2 glycans is a very common event in breast carcinogenesis. To determine if the change in glycosylation observed in breast carcinomas confers an advantage to cancer cells, murine mammary carcinoma cell lines were developed that express MUC1 carrying core 2 or core 1 linked glycans. The in vivo growth rate in wild-type and nude mice were identical regardless of the O-glycosylation patterns. However, the tumors that grew out of wild-type mice lost most of their MUC1 expression. In contrast, in MUC1 transgenic mice, where expression of MUC1 was retained by the tumor, a striking difference in growth rate was observed. In these mice, cells expressing core 1 glycans grew significantly faster than cells expressing core 2 glycans. These data suggest that MUC1 transgenic mice are more tolerant to core 1 expressing tumors than to tumors expressing core 2.
Mungul
Arron
A
Breast Cancer Biology, Thrid Floor Thomas Guy House, Guy's Hospital, London SE1 9RT, UK.
Cooper
Lucienne
L
Brockhausen
Inka
I
Ryder
Kenneth
K
Mandel
Ulla
U
Clausen
Henrik
H
Rughetti
Aurelia
A
Miles
David W
DW
Taylor-Papadimitriou
Joyce
J
Burchell
Joy M
JM
D000818:Animals; D045744:Cell Line, Tumor; D006031:Glycosylation; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000235:genetics / Q000502:physiology*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D012799:Sialyltransferases / Q000032:analysis / Q000502:physiology*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D018396:Mucin-1; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase