Regulation of CD44-hyaluronan interactions in Burkitt's lymphoma and Epstein-Barr virus-transformed lymphoblastoid B cells by PMA and interleukin-4.
In this study, we investigated the regulation of CD44-hyaluronan (HA) interactions in a panel of EBV+ Burkitt's lymphoma (BL) and lymphoblastoid B cell lines (B-LCL) generated by in vitro EBV transformation of normal human B cells. The results show that among B cell mitogens, phorbol 12-myristate 13-acetate (PMA) alone induced strong HA recognition in EBV+ BL-30/B95-8 cells. Among the cytokines that affect B cell growth and differentiation, IL-4 alone induced HA recognition in BL-30/B95-8 cells. Attempts to delineate the molecular mechanism for this increased HA adhesion in BL-30/B95-8 cells revealed an enhanced expression of CD44 H, isoforms containing V3, V6, and V9 exons, alterations in the splicing pattern of the V4 exon, and the increased electrophoretic mobility of the CD44 H protein. In contrast, the ability to recognize HA was not observed in B-LCL cells stimulated with either PMA or IL-4, even though these cells respond to IL-4, as observed by upregulation of CD23 expression. The molecular pathways that regulate CD44 expression and CD44-mediated HA binding may be selectively inactivated in B-LCL cells. These results may have implications with respect to the generation and spread of B cell tumors.
Kryworuchko
M
M
Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Gee
K
K
Diaz-Mitoma
F
F
Kumar
A
A
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002051:Burkitt Lymphoma; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D008970:Molecular Weight; D020033:Protein Isoforms; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation
D018960:Hyaluronan Receptors; D008934:Mitogens; D020033:Protein Isoforms; D014415:Tunicamycin; D015847:Interleukin-4; D006820:Hyaluronic Acid; D013755:Tetradecanoylphorbol Acetate