Cell growth and matrix invasion of EBV-immortalized human B lymphocytes is regulated by expression of α(v) integrins

Shuang Huang, Dwayne Stupack, Aihua Liu, David Cheresh, Glen R. Nemerow

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

α(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 virus (EBV), a human herpesvirus associated with several lymphoproliferative disorders in man, induces expression of α(v) integrins on transformed B lymphocytes. In the studies reported here, we show that EBV infection increases α(v), β3 and β5 integrin subunit mRNAs as well as upregulates the expression of the α(v)β3 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 α(v) integrin promoter. Treatment of EBV-transformed B cells with α(v) antisense oligonucleotides specifically reduced cell surface expression of α(v) integrins, inhibited cell growth in low serum, reduced cell invasion in matrigels and decreased expression of metalloprotease, MMP9. These studies indicate that α(v) integrins play a significant role in EBV-induced B-lymphocyte proliferation and invasion. Strategies to interfere with α(v) integrin expression and/or function may therefore be of potential value in the treatment of EBV-associated lymphoproliferative disorders.

Original languageEnglish (US)
Pages (from-to)1915-1923
Number of pages9
JournalOncogene
Volume19
Issue number15
DOIs
StatePublished - Apr 6 2000

Keywords

  • B lymphocytes
  • Epstein-Barr virus
  • Integrins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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