Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2005-10-5
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8809-17
pubmed:dateRevised
2010-11-18
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
pubmed:year
2005
pubmed:articleTitle
Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen).
pubmed:affiliation
Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey 07109, USA. rblumenthal@gscancer.org
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