title: Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis.
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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dallas
authors.forename: Guosheng
authors.initials: G
authors.lastname: Liu
authors.forename: Wei-Chiang
authors.initials: WC
authors.lastname: Chen
authors.forename: Susan N
authors.initials: SN
authors.lastname: Thomas
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.forename: David L
authors.initials: DL
authors.lastname: Huso
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000473:pathology* / Q000503:physiopathology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
chemical_list: D002272:Carcinoembryonic Antigen; D018960:Hyaluronan Receptors