Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Colonic Neoplasms
  • DNA, Complementary
  • Gene Transfer Techniques
  • Genetic Vectors
  • Liver Neoplasms
  • Lung Neoplasms
  • Mice
  • Mice, Inbred BALB C
  • Skin Neoplasms
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1

MeSH Major

  • Genetic Therapy
  • Neoplasms, Experimental
  • Neovascularization, Pathologic
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases

abstract

  • Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, is overexpressed in most solid tumors. On the basis of the knowledge that solid tumor growth beyond a small volume is critically dependent on angiogenesis, and that adenovirus (Ad) vectors can mediate efficient in vivo gene transfer and expression, we hypothesized that Ad-mediated transfer of a secreted form of the extracellular domain of the flt-1 VEGF receptor (Adsflt) would suppress tumor growth on a regional basis. To evaluate this concept, three tumor models were examined using a murine colon carcinoma cell line and syngeneic BALB/c mice. First, mice with preestablished splenic CT26.CL25 tumors and liver metastases were given Adsflt on AdNull intravenously and, after 15 days, spleens and livers were harvested to quantify tumor burden. Adslft-treated animals had minimal residual splenic tumors and liver metastases; in contrast, control animals had bulky splenic tumors and extensive liver metastases (p < 0.003). Second, mice with preestablished lung metastases showed a significant reduction in pulmonary metastases with regionally administered Adslft (intratracheal, p < 0.02) but not when the vector was systemically administered (intravenous, p > 0.9). Finally, mice with primary subcutaneous tumors treated with intratumoral administration of Adslft showed significant tumor suppression (p < 0.05) not observed in AdNull-treated mice or mice given Adslft intravenously (p > 0.3). We conclude that Ad-mediated in vivo regional delivery of a secreted form of the extracellular domain of the flt-1 VEGF receptor can effectively inhibit regional tumor growth, a strategy that may provide a means to control tumor growth within the treated organ without the risk of systemic antiangiogenesis.

publication date

  • April 10, 1998

has subject area

  • Adenoviridae
  • Animals
  • Colonic Neoplasms
  • DNA, Complementary
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Liver Neoplasms
  • Lung Neoplasms
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental
  • Neovascularization, Pathologic
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Skin Neoplasms
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/hum.1998.9.6-823

PubMed ID

  • 9581905

Additional Document Info

start page

  • 823

end page

  • 833

volume

  • 9

number

  • 6