CD44 v6 (C44Mab-9) Mouse Monoclonal Antibody recognizes endogenous levels of total CD44 protein containing the variant v6 exon.

Monoclonal antibody is produced by immunizing animals with recombinant protein specific to the human CD44 variant v3-v10. This antigen has been further characterized as corresponding to residues surrounding Phe404 of human CD44 protein, within the CD44 variant v6 exon.

CD44 is a type I transmembrane glycoprotein that mediates cell-cell and cell-matrix interaction through its affinity for hyaluronic acid (HA) and possibly through other parts of the extracellular matrix (ECM). CD44 is highly polymorphic, possesses a number of alternative splice variants and undergoes extensive post-translational modifications (1,2). Increased surface levels of CD44 are characteristic of T cell activation, and expression of the protein is upregulated during the inflammatory response. Research studies have shown that interactions between CD44 and HER2 are linked to an increase in ovarian carcinoma cell growth (1-3). CD44 interacts with ezrin, radixin, and moesin (ERM), linking the actin cytoskeleton to the plasma membrane and the ECM (4-6). CD44 is constitutively phosphorylated at Ser325 in resting cells. Activation of PKC results in phosphorylation of Ser291, dephosphorylation of Ser325, disassociation of ezrin from CD44, and directional motility (4).

Human CD44 consists of 19 exons, of which 10 are expressed in the standard isoform (CD44s) and all other isoforms. The nine variant exons (v2-v10) inserted between the constant regions via alternative splicing are the source of CD44 heterogeneity, and can dramatically alter the cell-adhesion properties of CD44-expressing cells (7-10). Expression of CD44 isoforms containing exon v6 is associated with metastasis and poor clinical outcomes in colorectal cancer, osteosarcoma, breast cancer, head and neck squamous cell carcinoma, endometriosis, and pancreatic carcinoma (11-16).

Among pancreatic ductal adenocarcinomas (PDAC) cell lines, those that highly express CD44v, including CD44 v6, exhibit an epithelial or MET phenotype, express E-cadherin, and have an increased growth rate (9). Conversely, PDAC cells that highly express CD44s exhibit a mesenchymal phenotype, have high gemcitabine resistance, and co-express proteins associated with EMT transition, including vimentin and ZEB-1 (9). In vivo, PDAC cells have the ability to switch between expression of these CD44 isoforms in response to chemotherapy, demonstrating the importance of CD44-targeted therapies for treatment of some cancers (9).