Abstract
αv 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 virus (EBV), a human herpesvirus associated with several lymphoproliferative disorders in man, induces expression of αv integrins on transformed B lymphocytes. In the studies reported here, we show that EBV infection increases αv, β3 and β5 integrin subunit mRNAs as well as upregulates the expression of the αvβ3 integrin protein on human B cells. 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 αv integrin promoter. Treatment of EBV-transformed B cells with αv antisense oligonucleotides specifically reduced cell surface expression of αv integrins, inhibited cell growth in low serum, reduced cell invasion in matrigels and decreased expression of metalloprotease, MMP9. These studies indicate that αv integrins play a significant role in EBV-induced B-lymphocyte proliferation and invasion. Strategies to interfere with αv integrin expression and/or function may therefore be of potential value in the treatment of EBV-associated lymphoproliferative disorders.
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Acknowledgements
This study was supported by NIH grants HL54352 and EY11431. This is Manuscript No. 12748-IMM at The Scripps Research Institute. We thank Catalina Hope for preparation of the manuscript.
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Huang, S., Stupack, D., Liu, A. et al. Cell growth and matrix invasion of EBV-immortalized human B lymphocytes is regulated by expression of αv integrins. Oncogene 19, 1915–1923 (2000). https://doi.org/10.1038/sj.onc.1203509
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DOI: https://doi.org/10.1038/sj.onc.1203509
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