BLOCKADE OF METASTASIS FORMATION BY CD44-RECEPTOR GLOBULIN

CD44 standard as well as variant isoforms have been frequently reporte d to be involved in the process of metastasis formation, Whereas in th e rat system, but also in some human tumours, the variant exon v6 is o f importance in the lymphatic spread of carcinomas, in human malignant melanoma CD44s and, possibly, CD44v10 appear to facilitate local inva sion and haematogenous spread. This has been tested in the B16F10 muri ne melanoma model by treating B16F10-bearing C57BL/6 mice either with a CD44s-/ CD44v10-specific antibody, or with receptor globulins (Rg) c ontaining the extracellular part of CD44s or CD44v10 linked to the con stant region of the immunoglobulin kappa light chain, Prior characteri zation of the CD44s and CD44v10 Rg had shown that both Rgs bound to co mponents of the extracellular matrix, CD44s in particular to hyaluroni c acid. Immunohistological screening of organ sections from adult C57B L/6 mice revealed additional evidence for both Rgs binding to elements of the extracellular matrix, particularly in bone marrow, intestine a nd lung, In the absence of any further treatment, the CD44s Rg reduced the number of lung colonies by 70%, while application of the CD44v10 Rg resulted in 60% reduction, CD44-specific antibodies were equally ef ficient with regard to B16F10 settlement in the lung. However, only th e CD44 Rgs prevented spread and settlement of melanoma cells in distan t organs. The finding confirms the involvement of both CD44s and CD44v 10 in melanoma progression, and is suggestive for the use of Rgs as th erapeutic reagents. (C) 1998 Wiley-Liss, Inc.