Document Detail


Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis.
MedLine Citation:
PMID:  22415308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Matthew R Dallas; Guosheng Liu; Wei-Chiang Chen; Susan N Thomas; Denis Wirtz; David L Huso; Konstantinos Konstantopoulos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-13
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-08-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2648-56     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD44 / physiology*
Carcinoembryonic Antigen / physiology*
Cell Movement / physiology
Colonic Neoplasms / pathology*,  physiopathology
Gene Knockdown Techniques
Gene Silencing
Humans
Liver Neoplasms / secondary
Lung Neoplasms / secondary
Mice
Neoplasm Metastasis / physiopathology*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
R01-CA-101135/CA/NCI NIH HHS; U54-CA-143868/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD44; 0/Carcinoembryonic Antigen
Comments/Corrections
Erratum In:
FASEB J.2012 Nov;26(11):4774

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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