A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells

Abstract

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.

The interaction of versican with its binding partners

“…CD44 can be altered by differential splicing of at least 10 variable exons encoding a segment of the extracellular domain, termed exons v1-v10, and by cell type-specific glycosylation [79]. CD44 has been shown to mediate cell-cell and cell-ECM interactions [80,81], augment tumor cell motility on hyaluronan-coated substrates [81,82], costimulate lymphocyte activation and tissue infiltration [83], and promote growth and metastasis of some tumor types [84,85]. Although GAG chains associated with some CD44 isoforms can also bind a subset of heparin-binding growth factors, cytokines, and ECM proteins such as fibronectin, most of the functions ascribed to CD44 can be attributed to its ability to bind to and internalize hyaluronan [38,86].…”

Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin

“…All of the CD44 variants (CD44v) contain insertions of various combinations of variant exons (1-10) located between exons 5 and 16 of the CD44 gene (Screaton et al, 1992(Screaton et al, , 1993. In contrast to merlin, which displays tumor-suppressor activity, CD44 promotes tumor invasion and metastasis (Gunthert et al, 1991;Sherman et al, 1994;Lamb et al, 1997;Yu et al, 1997;Stamenkovic, 1999, 2000).…”

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

“…Since it was discovered that the splice variant CD44v4-7 is involved in metastasis of tumor cells, 11 several studies have addressed the relevance of CD44 variant isoforms as diagnostic and prognostic markers for human tumors (reviewed by Herrlich et al 9 and Gü nthert et al 12 ). In multiple myeloma, CD44v9 expression in the absence of CD44v10 on bone marrow plasma cells is associated with a progressive phase of disease, 13 while CD44v9 expression on bone marrow biopsies of myeloma patients is correlated with an adverse prognosis.…”