Overexpression of MUC1 reconfigures the binding properties of tumor cells.
Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. MUC1 is overexpressed and aberrantly glycosylated by a variety of tumor cells. Studies described here examined whether tumor-associated MUC1 conferred new binding properties on tumor cell lines. Flow cytometry analysis with soluble P-, E- and L-selectin/IgM chimeric proteins was performed on human pancreatic (S2-013 and Panc-1) and colon (Caco-2) tumor cells. S2-013 cells bound E- and P-selectin and Caco-2 cells bound P-selectin. Epitope-tagged MUC1 (MUC1F) expressed by S2-013, Panc-1 and Caco-2 tumor cells did not bind to P-, E- or L-selectin. Overexpression of MUC1F on the surface of S2-013 cells blocked the interactions of E-selectin to tumor-associated ligand(s) but did not affect accessibility of monoclonal antibodies to other cell surface glycoproteins (CD9, CD44). Cell aggregation assays revealed that MUC1F expressed by S2-013 cells was able to bind to intracellular adhesion molecule-1 expressed on B cells. Overexpression of MUC1F containing a targeted mutation (the tandem repeat domain entirely or partially deleted) did not block the binding of E-selectin to its S2-013-associated ligand. These results demonstrate for the first time that the heavily O-glycosylated tandem repeat domain of MUC1 can simultaneously mediate and block binding to adhesion molecules with some molecular specificity and further support the hypothesis that MUC1 plays a dual role in the metastatic spread of tumor cells.
McDermott
K M
KM
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Crocker
P R
PR
Harris
A
A
Burdick
M D
MD
Hinoda
Y
Y
Hayashi
T
T
Imai
K
K
Hollingsworth
M A
MA
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D020080:Tandem Repeat Sequences; D014407:Tumor Cells, Cultured
D019040:E-Selectin; D018396:Mucin-1