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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3925-3934.
Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-09-3618.
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Submitted September 17, 2004
Accepted January 25, 2005
Transmembrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein-specific morphology and migration of endothelial cells
Mario M Muller, Bernhard B Singer, Esther Klaile, Bjorn Obrink, and Lothar Lucka*
Institut fur Biochemie und Molekularbiologie, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
Institut fur Biochemie und Molekularbiologie, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden
* Corresponding author; email: lothar.lucka{at}charite.de.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1/CD66a), expressed on leukocytes, epithelia and endothelia, mediates homophilic cell adhesion. It plays an important role in cell morphogenesis and recently, soluble CEACAM1-isoforms have been implicated in angiogenesis. In the present study, we investigated the function of transmembrane CEACAM1-L in cultured rat brain endothelial cells. We observed that expression of CEACAM1-L promotes network formation on basement membrane Matrigel and increased cell motility after monolayer injury. During cell-matrix adhesion, CEACAM1-L translocated into the Triton X-100-insoluble cytoskeletal fraction and affected cell spreading and cell morphology on Matrigel and laminin-1 but not on fibronectin. On laminin-1, CEACAM1-L expressing cells developed protrusions with lamellipodia, showed less stress fiber formation, reduced FAK tyrosine phosphorylation, and decreased focal adhesion formation leading to high motility. CEACAM1-L-mediated morphological alterations were sensitive to RhoA activation via LPA treatment and dependent on Rac1 activation. Furthermore, we demonstrate a matrix protein-dependent association of CEACAM1-L with talin, an important regulator of integrin function. Taken together, our results suggest that transmembrane CEACAM1-L expressed on endothelial cells is implicated in the activation phase of angiogenesis by affecting the cytoskeleton architecture and integrin-mediated signaling.

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