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Cell growth and matrix invasion of ebv-immortalized human b lymphocytes is regulated by expression of alpha(v) integrins

Academic Article
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Overview

authors

  • Huang, S.
  • Stupack, D.
  • Liu, A. H.
  • Cheresh, D.
  • Nemerow, Glen

publication date

  • April 2000

journal

  • Oncogene  Journal

abstract

  • 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 virus (EBV), a human herpesvirus associated with several lymphoproliferative disorders in man, induces expression of alpha(v) integrins on transformed B lymphocytes. In the studies reported here, we show that EBV infection increases alpha(v), beta3 and beta5 integrin subunit mRNAs as well as upregulates the expression of the alphavbeta3 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 alpha(v) integrin promoter. Treatment of EBV-transformed B cells with alpha(v) antisense oligonucleotides specifically reduced cell surface expression of alpha(v) integrins, inhibited cell growth in low serum, reduced cell invasion in matrigels and decreased expression of metalloprotease, MMP9. These studies indicate that alpha(v) integrins play a significant role in EBV-induced B-lymphocyte proliferation and invasion. Strategies to interfere with alphav integrin expression and/or function may therefore be of potential value in the treatment of EBV-associated lymphoproliferative disorders.

subject areas

  • Antigens, CD
  • B-Lymphocytes
  • Cell Division
  • Cell Line, Transformed
  • Epstein-Barr Virus Nuclear Antigens
  • Gene Expression Regulation, Viral
  • Herpesvirus 4, Human
  • Humans
  • Integrin alphaV
  • Integrins
  • Neoplasm Invasiveness
  • Oligonucleotides, Antisense
  • Transcriptional Activation
  • Viral Matrix Proteins
  • Viral Proteins
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Research

keywords

  • B lymphocytes
  • Epstein-Barr virus
  • integrins
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Identity

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1203509

PubMed ID

  • 10773881
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Additional Document Info

start page

  • 1915

end page

  • 1923

volume

  • 19

issue

  • 15

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