Cell growth and matrix invasion of EBV-immortalized human B lymphocytes isregulated by expression of alpha(v) integrins

alpha(v) Integrins have been shown to play an important role in epithelial- derived cell migration, cell growth and tumor invasion/metastasis, however their role on cells of hematopoietic origin is less clear. Epstein-Barr vir us (EBV), a human herpesvirus associated with several lymphoproliferative d isorders in man, induces expression of alpha(v) integrins on transformed B lymphocytes. In the studies reported here, we show that EBV infection incre ases alpha(v), beta(3) and beta(5) integrin subunit mRNAs as well as upregu lates the expression of the alpha(v)beta(3) integrin protein on human B cel ls. Among the nine different EBV proteins expressed in latently infected B cells (nuclear and plasma membrane-associated), only LMP1, LMP2A and EBNA2 were shown to selectively transactivate the alpha(v) integrin promoter. Tre atment of EBV-transformed B cells with alpha(v) antisense oligonucleotides specifically reduced cell surface expression of alpha(v) integrins, inhibit ed cell growth in low serum, reduced cell invasion in matrigels and decreas ed expression of metalloprotease, MMP9, These studies indicate that alpha(v ) integrins play a significant role in EBV-induced B-lymphocyte proliferati on and invasion. Strategies to interfere with alpha(v) integrin expression and/or function may therefore be of potential value in the treatment of EBV -associated lymphoproliferative disorders.