Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation.
OBJECTIVE
Neoplasia-related alterations in cell surface alpha(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-beta signaling gene Smad3 (Madh3) were tested for alpha(1,2)fucosylated glycan expression.


METHODS
Ulex europaeus agglutinin-I (UEA-I) lectin staining, fucosyltransferase gene Northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed.


RESULTS
Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express alpha(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of alpha(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3-targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knockout mice, UEA-I lectin staining was eliminated from colon and colon tumors; however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype.


CONCLUSIONS
In this model of colorectal cancer, cell surface alpha(1,2)fucosylation does not affect development of colon tumors.
Domino
Steven E
SE
Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, Mich., USA. sedomino@med.umich.edu
Karnak
David M
DM
Hurd
Elizabeth A
EA
D000818:Animals; D015152:Blotting, Northern; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000502:physiology*; D018095:Germ-Line Mutation; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D037121:Plant Lectins / Q000378:metabolism*; D051900:Smad3 Protein / Q000235:genetics*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D037121:Plant Lectins; D051900:Smad3 Protein; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C497791:Smad3 protein, mouse; C036850:Ulex europaeus lectins