Enhancement of metastatic properties of pancreatic cancer cells by MUC1 gene encoding an anti-adhesion molecule.
MUC1 mucin expression has been shown to be associated clinicopathologically with metastasis and poor clinical outcome in a variety of tumors. To further investigate this finding experimentally, human pancreatic cancer S2-013 cells overexpressing MUC1 were used for spontaneous metastatic potential in nude mice. It was found that the number of lung metastases of MUC1 transfectants was significantly higher than that of control cells. To analyze the molecular mechanisms that underlie the increased metastatic activity, in vitro adhesion assays were performed. MUC1 mucin expression enhancedin vitro invasiveness and motility of S2-013 cells, and decreased the binding of S2-013 cells to type I collagen, Type IV collagen and laminin. Similar effects were not observed for cells expressing tandem repeat-deleted MUC1 cDNA. Adhesion properties were abolished by benzyl-alpha-GalNAc treatment, indicating that glycosylation of the extracellular domain of MUC1 was essential for these biological adhesive functions. Our data support the hypothesis that MUC1 expression contributes to the metastatic ability of pancreatic cancer cells.
Satoh
S
S
The First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hinoda
Y
Y
Hayashi
T
T
Burdick
M D
MD
Imai
K
K
Hollingsworth
M A
MA
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D001593:Benzyl Compounds / Q000633:toxicity; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics* / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D001593:Benzyl Compounds; D016326:Extracellular Matrix Proteins; D018396:Mucin-1; D011994:Recombinant Proteins; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine