Expression of functional very late Antigen-α1, -α2, -α3 and -α6 integrins on Ewing's sarcoma and primitive peripheral neuroectodermal tumour cells and modulation by interferon-γ and tumour necrosis factor-α

F. van Valen, H. Hanenberg, H. Jürgens

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Twelve different human primary and metastatic Ewing's sarcoma (ES) and primitive peripheral neuroectodennal tumour (pPNET) cell lines were examined by fluorocytometric analysis for the expression of α1, α2, α3 and α6 very late antigen (VLA) β1-integrins. VLA-α1, was abundantly expressed on all typical ES cell lines and pPNET cell lines, while absent from atypical (large cell) ES cells. VLA-α2 was displayed on some ES and pPNET cell lines. In two different pPNET cell lines, derived from the same patient, VLA-α2 expression was considerably higher on primary cells compared with metastatic cells. VLA-α3 was exclusively expressed on pPNET cell lines. Expression of VLA-α6 was higher on metastatic than on primary ES and pPNET cells. Adhesion assays on purified extracellular matrix (ECM) proteins, using monospecific adhesion-blocking antibodies, disclosed VLA-1 (α1β1) on typical ES cells and pPNET cells, and VLA-2 (α2β1) on atypical ES cells, as dual collagen type IV (COIV)/laminin (LM) binding sites, and VLA-6 (α6β1) as a specific LM binding site. Treatment of typical ES cells and pPNET cells for up to 48 h with recombinant human interferon-γ (rhIFNγ) and tumour necrosis factor-α (rhTNFα) upregulated α1 and β1 expression, concomitant with an increase in cell adhesion to COIV and LM. Alternatively, these cytobines downregulated the expression of α2, α6 and β1 on atypical ES cells, concomitant with a decrease in the adhesion to COIV and LM. In conclusion, these findings suggest that the difference in repertory of CO and LM integrin receptors on ES cells and pPNET cells reflects tumour status and degree of differentiation. Furthermore, our data indicate that IFNγ- and TNFα-mediated alteration in the level of expression of distinct VLAs on ES and pPNET cells is correlated with changes in the adhesive behaviour of these tumour cells.

Original languageEnglish (US)
Pages (from-to)2119-2125
Number of pages7
JournalEuropean Journal of Cancer
Volume30
Issue number14
DOIs
StatePublished - 1994

Keywords

  • Ewing's sarcoma cells
  • collagen
  • integrins
  • laminin
  • primitive peripheral neuroectodermal tumour cells
  • tumour cell adhesion
  • very late antigen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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