Wolfgang Rudy

A NEW VARIANT OF GLYCOPROTEIN CD44 CONFERS METASTATIC POTENTIAL TO RAT CARCINOMA CELLS

Using a monoclonal antibody (MAb1.1ASML) raised against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, cDNA clones have been isolated that encode glycoproteins with partial homology to CD44, a presumed adhesion molecule. In one of the clones, pMeta-1, the epitope marks an additional extracellular domain of 162 amino acids inserted into the rat CD44 protein between amino acid positions 223 and 247 (by analogy to human and murine CD44). The new variants are expressed only in the metastasizing cell lines of two rat tumors, the pancreatic carcinoma BSp73 and the mammary adenocarcinoma 13762NF; they are not expressed in the non-metastasizing tumor cell lines nor in most normal rat tissues. Overexpression of pMeta-1 in the nonmetastasizing BSp73AS cells suffices to establish full metastatic behavior.

Cd44 and Splice Variants of Cd44 in Normal Differentiation and Tumor Progression

CD44, originally defined by antibodies as a leukocyte surface protein (reviewed in Haynes et al., 1989), has become a polymorphic family of proteins expressed in various cells and conditions. The polymorphism is due to differential modifications and to splice variation (Hughes et al., 1983; Omary et al., 1988; Kansas et al., 1989; Picker et al., 1989; Goldstein et al., 1989; Goldstein and Butcher, 1990; Stamenkovic et al., 1991, Dougherty et al., 1991; Brown et al., 1991; Gunthert et al., 1991; Shtivelman and Bishop, 1991; Jackson et al., 1992). Because of the polymorphism a multitude of functions can be expected. Yet these need t be defined. All or part of the CD44 glycoproteins have affinity for hyaluronic acid, some forms are linked to chondoitin sulfate and bind fibronectin and collagen (Aruffo et al., 1990; Miyake et al., 1990; Stamenkovic et al., 1989; Goldstein et al., 1989; Wolffe et al. 1990; Carter and Wayner, 1988; Jalkanen and Jalkanen, 1992). These affinnites may have functions in association with different primary structures domains introduced by splice variation.