Source:http://linkedlifedata.com/resource/pubmed/id/16204051
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
19
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pubmed:dateCreated |
2005-10-5
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pubmed:abstractText |
CEACAM5 and CEACAM6 are overexpressed in many cancers and are associated with adhesion and invasion. The effects of three monoclonal antibodies targeting different epitopes on these antigens (NH2-terminal [MN-3] and A1B1 domains [MN-15] shared by CEACAM5 and CEACAM6 and the A3B3 domain [MN-14] restricted to CEACAM5) were evaluated in migration, invasion, and adhesion assays in vitro using a panel of human pancreatic, breast, and colonic cancer cell lines, and in the GW-39 human colonic micrometastasis model in vivo. MN-3 Fab' and MN-15 Fab' were both effective at inhibiting cell migration. MN-15 Fab' treatment inhibited invasion, reducing cell penetration through an extracellular matrix (ECM). MN-3 Fab' also decreased invasion but was less effective than MN-15 Fab' in four of five cell lines. All three monoclonal antibody (mAb) Fabs decreased adhesion of tumor cells to endothelial cells by 49% to 58%. MN-15 Fab' but not MN-3 or MN-14 Fabs induced a decrease in adhesion of three of six cell lines to the ECM protein, fibronectin, but adhesion to vitronectin, laminin, collagen-I, and collagen-IV was not affected. In vivo studies showed that treatment with MN-3 Fab' or MN-15 Fab' of mice implanted with GW-39 human colonic cancer cells increased their survival (P < 0.025 and P < 0.01, respectively). These studies show that antibody Fabs that target either CEACAM5 or CEACAM6 affect cell migration, cell invasion, and cell adhesion in vitro, and that MN-15 and MN-3 Fabs have antimetastatic effects in vivo, resulting in improved survival of mice with metastases. Thus, blocking the N and A1B1 domains of CEACAM5/CEACAM6 can impede the metastatic process.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/CEACAM6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8809-17
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16204051-Animals,
pubmed-meshheading:16204051-Antibodies,
pubmed-meshheading:16204051-Antigens, CD,
pubmed-meshheading:16204051-Carcinoembryonic Antigen,
pubmed-meshheading:16204051-Cell Adhesion,
pubmed-meshheading:16204051-Cell Adhesion Molecules,
pubmed-meshheading:16204051-Cell Line, Tumor,
pubmed-meshheading:16204051-Cell Movement,
pubmed-meshheading:16204051-Colonic Neoplasms,
pubmed-meshheading:16204051-Endothelial Cells,
pubmed-meshheading:16204051-Female,
pubmed-meshheading:16204051-GPI-Linked Proteins,
pubmed-meshheading:16204051-Humans,
pubmed-meshheading:16204051-Lung Neoplasms,
pubmed-meshheading:16204051-Mice,
pubmed-meshheading:16204051-Mice, Nude,
pubmed-meshheading:16204051-Neoplasm Invasiveness,
pubmed-meshheading:16204051-Neoplasm Metastasis,
pubmed-meshheading:16204051-Neoplasms,
pubmed-meshheading:16204051-Xenograft Model Antitumor Assays
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pubmed:year |
2005
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pubmed:articleTitle |
Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen).
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pubmed:affiliation |
Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey 07109, USA. rblumenthal@gscancer.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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