REGULATION OF GROWTH ACID DISSEMINATION OF A HUMAN LYMPHOMA BY CD44 SPLICE VARIANTS

CD44 is a polymorphic cell surface glycoprotein, currently proposed to be the principal cell surface receptor for hyaluronan, However, diffe rent isoforms of CD44, expressed in human lymphoid tumor cells, appear to have distinct effects on the ability of the cells to attach to hya luronan-coated surfaces and on their capacity to form tumors in vivo, In the present study, we address the mechanisms that may regulate CD44 isoform-dependent adhesion to hyaluronan. We use a human Burkitt lymp homa, stably transfected with six different alternatively spliced huma n CD44 isoforms, to determine their potential hyaluronan binding and t umor growth promoting roles, We show that transfectants expressing CD4 4 splice variants that contain variable exons 6-10, 7-10 and 8-10 adhe re to hyaluronan-coated surfaces weakly and that corresponding tumor f ormation in vivo is delayed with respect to CD44-negative parental cel l-derived tumors. Abundant shedding of these three isoforms may play a significant role in determining the rate of tumor development, Transf ectants expressing variable exon 3, on the other hand, fail to display CD44-mediated adhesion to hyaluronan, but form bone marrow tumors rap idly following intravenous injection. These observations suggest that different mechanisms regulate CD44-mediated adhesion and tumor growth, and provide evidence that expression of exon v3 may confer novel liga nd-binding properties.