Helmut Ponta¹ and Peter Herrlich^1,2

1 Forschungszentrum Karlsruhe, Institute of Genetics, and ² University of Karlsruhe, Institute of Genetics, Postfach 3640, D-76021 Karlsruhe, Germany

Received 4/27/98 Accepted 5/12/98

4. PERSPECTIVES

Members of the CD44 protein family containing variant exon sequences are involved in tumor progression and metastasis formation and are thus targets for diagnosis and therapy. Understanding of their molecular function and the regulation of alternative splicing that accounts for variant exon inclusion is pivotal for the development of effective therapeutic regiments. The mechanism of presentation of growth factor by a CD44 variant located on the ectodermal cells in the limb to high affinity receptors on mesenchymal cells to keep them in proliferation is the first example of a molecular action of a CD44 variant in vivo. Inhibition of limb outgrowth by CD44 variant specific antibodies and the retardation of tumor metastasis formation by the same antibodies suggest that the mode of action of CD44 variants in tumor progression might also involve a growth factor presentation mechanism.