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PMID: 15509546 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CEACAM1 enhances invasion and migration of melanocytic and melanoma cells.

The American journal of pathology ·Vol. 165 ·No. 5 ·2004-11-00 ·Pages 1781-7

Ebrahimnejad A, Streichert T, Nollau P, Horst AK, Wagener C, Bamberger AM, Brümmer J

Abstract

Expression of the cell adhesion molecule CEACAM1 in melanomas is an independent factor for the risk of metastasis with a predictive value superior to that of tumor thickness. We have previously shown that CEACAM1 co-localizes at the tumor-stroma interface of invading melanoma masses with integrin beta(3) and that these two adhesion molecules interact via the CEACAM1 cytoplasmic domain. To address the functional consequences of CEACAM1 expression, we investigated invasion and migration of melanocytic and melanoma cells that stably express CEACAM1 using two different in vitro systems. Here, we demonstrate that CEACAM1 expression markedly enhances cell invasion and migration. The enhanced invasion and migration of CEACAM1-transfected cells was dependent on the presence of Tyr-488 within the full-length cytoplasmic CEACAM1 domain. Treatment with anti-CEACAM monoclonal antibodies blocked CEACAM1-enhanced cell invasion and cell migration in a dose-dependent manner. Furthermore, the enhanced invasion and migration of CEACAM1-transfected melanoma cells was blocked by integrin-antagonizing RGD peptides. Expression of integrin beta(3) induces the up-regulation of CEACAM1 in melanocytic MEL6 cells. These results strengthen the view that CEACAM1 and alpha(v)beta(3) integrin are functionally interconnected with respect to the invasive growth of melanomas.

MeSH Terms
Antibodies, Monoclonal/chemistry Antigens, CD/physiology Antigens, Differentiation/physiology Blotting, Western Cell Adhesion Cell Adhesion Molecules Cell Line, Tumor Cell Movement Cytoplasm/metabolism DNA, Complementary/metabolism Dose-Response Relationship, Drug Humans Integrin alphaVbeta3/metabolism Integrin beta3/metabolism Melanocytes/metabolism Melanoma/metabolism Neoplasm Invasiveness Neoplasm Metastasis Oligonucleotide Array Sequence Analysis Oligopeptides/chemistry Protein Structure, Tertiary Time Factors Transfection Tyrosine/chemistry Up-Regulation
Chemicals
Antibodies, Monoclonal Antigens, CD Antigens, Differentiation CD66 antigens Cell Adhesion Molecules DNA, Complementary Integrin alphaVbeta3 Integrin beta3 Oligopeptides Tyrosine arginyl-glycyl-aspartic acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ebrahimnejad Alireza
Institute of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany.
Streichert Thomas
Nollau Peter
Horst Andrea K
Wagener Christoph
Bamberger Ana-Maria
Brümmer Jens
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63433-5
Published
2004-11-00
Pages
1781-7
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1618678
Subset
IM
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63433-5 PMC Full Text View journal details
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