CEACAM1 enhances invasion and migration of melanocytic and melanoma cells.
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.
Ebrahimnejad
Alireza
A
Institute of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany.
Streichert
Thomas
T
Nollau
Peter
P
Horst
Andrea K
AK
Wagener
Christoph
C
Bamberger
Ana-Maria
AM
Brümmer
Jens
J
D000911:Antibodies, Monoclonal / Q000737:chemistry; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D009842:Oligopeptides; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid