Cleavage of carcinoembryonic antigen induces metastatic potential in colorectal carcinoma.

Abstract:

:Carcinoembryonic antigen (CEA), a widely used tumor marker, is attached by a glycosylphosphatidylinositol (GPI) anchor motif to the cell membrane. Recent study suggested that membrane-bound CEA might be cleaved by glycosylphosphatidylinositol-phospholipase D (GPI-PLD). We studied the effect of GPI-PLD on the cleavage of CEA to elucidate the implication for metastatic potential in colorectal carcinoma cells. CEA amount of conditioned medium was changed by suramin and phenanthroline (activator and inhibitor of GPI-PLD) only in SW620 and SW837 which expressed both CEA and GPI-PLD mRNA. Suramin treatment also augmented migratory activity and decreased cell surface CEA expression in SW620 and SW837. Furthermore, GPI-PLD knockdown cells using GPI-PLD-specific siRNA in SW620 and SW837 showed decreased CEA secretion from cell membrane and the migration activity, increased membrane-bound CEA amount. Splenic injection of SW620 and SW837 induced marked hepatic metastases in nude mice. These results suggest that membrane-bound CEA is cleaved by GPI-PLD and that this cleavage enhances the metastatic potential in colorectal carcinoma cells.

authors

Yamamoto Y,Hirakawa E,Mori S,Hamada Y,Kawaguchi N,Matsuura N

doi

10.1016/j.bbrc.2005.05.084

subject

Has Abstract

pub_date

2005-07-22 00:00:00

pages

223-9

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)01080-6

journal_volume

333

pub_type

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