CEACAM1 Enhances Invasion and Migration of Melanocytic and Melanoma Cells

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 ␤ 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 CEACAM1enhanced cell invasion and cell migration in a dosedependent manner. Furthermore, the enhanced invasion and migration of CEACAM1-transfected melanoma cells was blocked by integrin-antagonizing RGD peptides. Expression of integrin ␤ 3 induces the up-regulation of CEACAM1 in melanocytic MEL6 cells. These results strengthen the view that CEACAM1 and ␣ v ␤ 3 integrin are functionally interconnected with respect to the invasive growth of melanomas.

Novel Immunotherapy for Malignant Melanoma with a Monoclonal Antibody That Blocks CEACAM1 Homophilic Interactions

“…Importantly, 49 of 55 cultures (89%) were significantly stained (Fig. 1A), while it is known that CEACAM1 is not expressed by normal melanocytes (27). Moreover, the presence of CEACAM1 þ lymphocytes was shown in the vicinity of a representative CEACAM1 þ melanoma metastasis to a lymph node (Fig.…”

“…The clinical and biologic evidence highlight CEACAM1 as a rational target for immunotherapy: CEACAM1 is not found on normal melanocytes (27) but undergoes neoexpression and is widely expressed on the vast majority of metastatic melanoma specimens (Fig. 1A).…”

Corticotropin-Releasing Hormone Modulates Human Trophoblast Invasion through Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulation

“…This effect was dependent on integrins, and a functional role of CEACAM1-integrin ␤3 interaction in cellular invasion was suggested. 26 Furthermore, paxillin, a key protein of focal adhesions, has been shown to associate with CEACAM1 in granulocytes, epithelial cells, and human umbilical vein endothelial cells.…”

“…26 As negative control for the transfection experiments (mock), the expression vector pcDNA3.1(Ϫ) (Invitrogen, Karlsruhe, Germany) was used. To demonstrate that the transfections were successful, cells were analyzed by Western blot and immunocytochemistry.…”

CEACAM1 : modulateur central du métabolisme, de la progression tumorale,de l’angiogenèse et de l’immunité

“…D'autre part, bien que CEACAM1 ne soit pas exprimée dans la glande thyroïde normale ou dans ses tumeurs bénignes, elle est surexprimée dans les carcinomes thyroïdiens de nature métasta-tique [17]. Le mécanisme dans ce cas impliquerait l'augmentation des interactions de CEACAM1 avec la matrice extracellulaire, alors que dans les cancers pulmonaires et les mélanomes, la surexpression de CEACAM1 induirait un accroissement de la densité vasculaire [18,19].…”