Human CEACAM-6/CD66c Alexa Fluor® 647-conjugated Antibody

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM-6), previously called nonspecific cross‑reacting antigen (NCA) or CD66c, is one of seven human CEACAM family members within the immunoglobulin superfamily (1-4). In humans, CEACAMs include type I transmembrane proteins (CEACAM-1, -3, and -4) and Glycosylphosphatidylinositol (GPI)-linked molecules (CEACAM-5 through -8) (1). There is no human CEACAM-2. Human CEACAM-6 is a 90 kDa, GPI-linked membrane protein that contains a 34 amino acid (aa) signal sequence, a 286 aa extracellular domain (ECD), and a 24 aa hydrophobic C-terminal propeptide. The GPI membrane anchor is attached at the C-terminus following cleavage of the propeptide. CEACAM-6 contains one N-terminal V-type Ig-like domain (N domain), followed by two C2-type Ig-like domains (2-4). It shows considerable glycosylation, including (sialyl) Lewis^X, which mediates binding to E-Selectin, Galectins and some bacterial fimbrae (1, 2). Mature human CEACAM-6 shows 84%, 85%, 80%, 87% and 51% aa identity to the equivalent extracellular regions of human CEACAMs -1, -5 (CEA) and -8, rhesus CEACAM-2, and bovine CEACAM-6, respectively. CEACAM-6 is expressed by granulocytes and their precursors. Activation enhances surface expression by mobilizing CEACAM-6 from storage in azurophilic granules (5, 6). It often shows aberrant expression in acute lymphocytic leukemias (10). CEACAM-6 is also expressed in epithelia of various organs and is upregulated in pancreatic and colon adenocarcinomas and hyperplastic polyps (7, 8). Over-expression confers resistance to adhesion-related apoptosis (anoikis) in tumor cells (8, 9). CEACAM-6 is an intercellular adhesion molecule, forming both homotypic, and heterotypic bonds with CEACAM-1, -5 and -8 through interaction of the V-type Ig-like domains (11, 12). Cross-linking of neutrophil CEACAM-6 augments Integrin alpha_v beta₃ and beta₂-mediated adhesion, apparently by Src and Caveolin-mediated inside-out Integrin activation (8, 13, 14).