GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin α5β1-fibronectin interaction
✍ Scribed by Cosme Ordonez; Alexander B. Zhai; Pilar Camacho-Leal; Luisa Demarte; Mannie M.Y. Fan; Clifford P. Stanners
- Book ID
- 102312152
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 362 KB
- Volume
- 210
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Carcinoembryonic antigen (CEA) and CEA family member CEACAM6 are glycophosphatidyl inositol (GPI)‐anchored, intercellular adhesion molecules that are up‐regulated in a wide variety of human cancers, including colon, breast, and lung. When over‐expressed in a number of cellular systems, these molecules are capable of inhibiting cellular differentiation and anoikis, as well as disrupting cell polarization and tissue architecture, thus increasing tumorigenicity. The present study shows that perturbation of the major fibronectin receptor, integrin α5β1, underlies some of these biological effects. Using confocal microscopy and specific antibodies, CEA and CEACAM6 were demonstrated to co‐cluster with integrin α5β1 on the cell surface. The presence of CEA and CEACAM6 was shown to lead to an increase in the binding of the integrin α5β1 receptor to its ligand fibronectin, without changing its cell surface levels, resulting in increased adhesion of CEA/CEACAM6‐expressing cells to fibronectin. More tenacious binding of free fibronectin to cells led to enhanced fibronectin matrix assembly and the formation of a polymerized fibronectin “cocoon” around the cells. Disruption of this process with specific monoclonal antibodies against either fibronectin or integrin α5β1 led to the restoration of cellular differentiation and anoikis in CEA/CEACAM6 producing cells. J. Cell. Physiol. 210: 757–765, 2007. © 2006 Wiley‐Liss, Inc.