Recombinant Porcine CD44 Fc Chimera Protein, CF

CD44 is a ubiquitously expressed protein that is the major receptor for hyaluronan and exerts control over cell growth and migration (1 ‑ 5). Porcine CD44 is a type I transmembrane protein with a variable‑length extracellular domain (ECD) that contains a 100 amino acid (aa) hyaluronan‑binding disulfide‑stabilized link region and a 48 ‑ 463 aa stem region. Within the stem, variably spliced exons produce multiple protein isoforms (1 ‑ 5). The shortest form does not include the variable segments, and is called the standard or hematopoietic form in humans (1 ‑ 5). In humans, cancer aggressiveness and T cell activation have been correlated with expression of specific isoforms (2, 4). With variable N- and O‑glycosylation and splicing within the stalk, CD44 can range from 80 to 200 kDa (1, 2). Within the ECD of CD44, porcine CD44 (aa 33 ‑ 234) shares 74 ‑ 81% aa sequence identity with the corresponding mouse, human and rat CD44 sequence. The many reported functions of CD44 fall within three categories (1, 2). First, CD44 binds hyaluronan and other ligands within the extracellular matrix and can function as a “platform” for growth factors and metalloproteinases. Second, CD44 is a co‑receptor that modifies activity of receptors including MET and the ErbB family of tyrosine kinases. Third, the CD44 intracellular domain links the plasma membrane to the actin cytoskeleton via the ERM proteins, ezrin, radixin and moesin. CD44 can be synthesized in a soluble form (4) or may be cleaved at multiple sites by either membrane‑type matrix metalloproteinases, or ADAM proteases to produce soluble ectodomains (6, 7). The cellular portion may then undergo gamma secretase‑dependent intramembrane cleavage to form an A beta ‑like transmembrane portion and a cytoplasmic signaling portion that affects gene expression (8, 9). These cleavage events are thought to promote metastasis by enhancing tumor cell motility and growth (1, 2, 6). In pigs, CD44 expressed on cumulus cells plays a key role in oocyte maturation through hyaluronan binding in the cumulus‑oocyte complex (10).