Reduction of tumor cell migration and metastasis by adenoviral gene transfer of plasminogen activator inhibitors

M. Praus, K. Wauterickx, D. Collen, R. D. Gerard

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Recombinant adenoviral vectors expressing u-PA, t-PA, PAI-1 and PAI-2 were employed to correlate the expression of components of the fibrinolytic system with the invasiveness of HT 1080 tumor cells. Migration through Transwell inserts in vitro in the presence of plasminogen was increased up to 22% by overexpression of u-PA, whereas t-PA had no effect. Gene transfer of PAI-1 or PAI-2 both reduced migration in a dose-dependent manner by up to 43% with PAI-1 and 29% with PAI-2. Two routes of gene transfer were used to alter metastasis of subcutaneously implanted HT 1080 cells expressing firefly luciferase in nude mice. Infection of cultured tumor cells with adenovirus expressing either PAI-1 or PAI-2 before implantation significantly reduced the incidence of lung metastasis by 60% compared with control virus. However, only PAI-2 reduced the incidence of lung and brain metastasis following liver gene transfer. Although PAI gene transfer by either route reduced primary tumor size, it had little effect on tumor vascularization or host survival. The migratory and metastatic phenotype of HT 1080 tumor cells is thus directly dependent on u-PA expression levels and can be altered by gene transfer of u-PA or plasminogen activator inhibitors.

Original languageEnglish (US)
Pages (from-to)227-236
Number of pages10
JournalGene Therapy
Volume6
Issue number2
DOIs
StatePublished - Feb 1 1999

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Keywords

  • Adenovirus
  • Gene transfer
  • Metastasis
  • Plasminogen activator

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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