Gene transfer of the vascular endothelial growth factor receptor flt-1 suppresses pulmonary metastasis associated with lung growth. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Gene Transfer Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pneumonectomy
  • Tumor Cells, Cultured
  • beta-Galactosidase

MeSH Major

  • Adenocarcinoma
  • Colonic Neoplasms
  • Genetic Therapy
  • Lung Neoplasms
  • Neovascularization, Pathologic
  • Vascular Endothelial Growth Factor Receptor-1

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 beta-galactosidase (betagal)-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 betagal 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 x 10(8) 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.

publication date

  • December 2005

has subject area

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Colonic Neoplasms
  • Gene Transfer Techniques
  • Genetic Therapy
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic
  • Pneumonectomy
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1
  • beta-Galactosidase

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2005-0092OC

PubMed ID

  • 16151052

Additional Document Info

start page

  • 629

end page

  • 635

volume

  • 33

number

  • 6