Journal
CANCER RESEARCH
Volume 67, Issue 21, Pages 10222-10229Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-2483
Keywords
-
Categories
Funding
- NCI NIH HHS [P30CA36727, CA09476, R01CA57362] Funding Source: Medline
Ask authors/readers for more resources
Perineural invasion in pancreatic adenocarcinoma, a common pathologic phenomenon whereby cancer cells invade and intimately contact the endoneurium of pancreatic nerves, is thought to contribute to both pain and local disease recurrence. MUC1, a type I transmembrane mucin that can affect the adhesive properties of cells, contains a large extracellular tandem repeat domain, which is heavily glycosylated in normal epithelia, but is overexpressed and differentially glycosylated in pancreatic cancer. This altered glycosylation includes the shortened core I O-glycans for monosialyl and disialyl T antigens. Myelin-associated glycoprotein (MAG), a membrane-bound protein expressed on oligodendrocytes and Schwann cells, binds myelin to neurons. MAG's preferred ligands are derivatives of the monosialyl and disialyl T antigen. We investigated whether MUC1 is a counter-receptor for MAG and if their interaction contributed to pancreatic perineural invasion. Results showed that MAG binds pancreatic cells expressing MUC1, that this binding is sialidase-sensitive, and that MAG physically associates with MUC1 Heterotypic adhesion assays between pancreatic cancer cells and Schwarm cells revealed that increased expression of MUC1 or MAG enhanced adhesion. Conversely, specific inhibition of MAG or sialyl-T MUC1 partially blocked adhesion. Inummohistochemical analysis of pancreatic perineural invasion showed the expression of both MUC1 and MAG. These results support the hypothesis that the adhesive interactions between MUC1 and MAG are of biological significance in pancreatic cancer perineural invasion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available