Gene transfer of the vascular endothelial growth factor receptor flt-1 suppresses pulmonary metastasis associated with lung growth

Masahiro Mae, Timothy P. O'Connor, Ronald G. Crystal

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Growth of solid tumor metastases is critically dependent on angiogenesis. We hypothesized that an "angiogenic-rich" milieu, as in pneumonectomy-induced lung growth, would be conducive to growth of pulmonary metastases, and that transfer of an antiangiogenic gene would suppress tumor growth. Two weeks after left pneumonectomy in BALB/c mice, right lung mass increased 1.5-fold compared with controls (P < 0.0001). Our pulmonary metastases model, intravenous administration of β-galactosidase (βgal)-marked CT26.CL25 colon carcinoma cells, resulted in diffuse metastases at 12 d after administration. However, if left pneumonectomy was performed 1 d before tumor cell administration, right lung mass was increased 1.7-fold after 12 d (P < 0.001 compared with the right + left lung of controls), and βgal activity was greater (2.8-fold, P < 0.05). To assess antiangiogenesis therapy, tumor cells were administered 1 d after pneumonectomy and 1 d later, 5 × 108 plaque-forming units of Adsflt (an Ad vector expressing the extracellular portion of the flt-1 vascular endothelial growth factor [VEGF] receptor) was administered. Compared with controls, mice receiving Adsflt via intranasal or intravenous routes showed suppression of pneumonectomy-induced tumor growth (P < 0.01, both routes compared with controls). Postpneumonectomy lung growth enhances growth of lung metastases, but this can be suppressed with Adsflt antiangiogenesis therapy.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume33
Issue number6
DOIs
Publication statusPublished - 1 Dec 2005

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Keywords

  • Adenovirus-mediated gene therapy
  • Antiangiogenesis
  • Compensatory lung growth
  • Lung metastasis
  • Pneumonectomy

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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