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FASEB J. 2012 Jun;26(6):2648-56. doi: 10.1096/fj.12-203786. Epub 2012 Mar 13.

Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis.

Author information

1
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.

Erratum in

  • FASEB J.2012 Nov;26(11):4774.

Abstract

After separating from a primary tumor, metastasizing cells enter the circulatory system and interact with host cells before lodging in secondary organs. Previous studies have implicated the surface glycoproteins CD44 and carcinoembryonic antigen (CEA) in adhesion, migration, and invasion, suggesting that they may influence metastatic progression. To elucidate the role of these multifunctional molecules while avoiding the potential drawbacks of ectopic expression or monoclonal antibody treatments, we silenced the expression of CD44 and/or CEA in LS174T colon carcinoma cells and analyzed their ability to metastasize in 2 independent mouse models. Quantitative PCR revealed that CD44 knockdown increased lung and liver metastasis >10-fold, while metastasis was decreased by >50% following CEA knockdown. These findings were corroborated by in vitro experiments assessing the metastatic potential of LS174T cells. Cell migration was decreased as a result of silencing CEA but was enhanced in CD44-knockdown cells. In addition, CD44 silencing promoted homotypic aggregation of LS147T cells, a phenotype that was reversed by additional CEA knockdown. Finally, CD44-knockdown cells exhibited greater mechanical compliance than control cells, a property that correlates with increased metastatic potential. Collectively, these data indicate that CEA, but not CD44, is a viable target for therapeutics aimed at curbing colon carcinoma metastasis.

PMID:
22415308
PMCID:
PMC3360151
DOI:
10.1096/fj.12-203786
[Indexed for MEDLINE]
Free PMC Article

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