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(American Journal of Pathology. 2004;165:1781-1787.)
© 2004 American Society for Investigative Pathology

CEACAM1 Enhances Invasion and Migration of Melanocytic and Melanoma Cells

Alireza Ebrahimnejad*, Thomas Streichert*, Peter Nollau*, Andrea K. Horst*, Christoph Wagener*, Ana-Maria Bamberger{dagger} and Jens Brümmer*

From the Institutes of Clinical Chemistry* and Gynecopathology,{dagger} University Hospital Eppendorf, Hamburg, Germany

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 ß3 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 ß3 induces the up-regulation of CEACAM1 in melanocytic MEL6 cells. These results strengthen the view that CEACAM1 and {alpha}vß3 integrin are functionally interconnected with respect to the invasive growth of melanomas.




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