In vivo gene transfer of pigment epithelium-derived factor inhibits tumor growth in syngeneic murine models of thoracic malignancies. Academic Article Article uri icon

Overview

MeSH

  • Adenoviruses, Human
  • Animals
  • Carcinoma, Squamous Cell
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Genetic Vectors
  • Injections, Intravenous
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Models, Cardiovascular
  • Protein Biosynthesis
  • Survival Analysis
  • Tumor Cells, Cultured

MeSH Major

  • Eye Proteins
  • Gene Transfer Techniques
  • Nerve Growth Factors
  • Proteins
  • Serpins
  • Thoracic Neoplasms

abstract

  • Pigment epithelium-derived factor is known to be an inhibitor of angiogenesis. We hypothesized that in vivo gene transfer of pigment epithelium-derived factor may inhibit tumor angiogenesis and growth in syngeneic models of thoracic malignancies. An adenovirus vector encoding the human pigment epithelium-derived factor cDNA (AdPEDF) was used to transduce human lung cancer cells in vitro. Transgene expression was assessed using Western analysis. Three different murine flank tumors (2 lung, 1 colon) were then established in syngeneic mice and treated intratumorally with phosphate-buffered saline, AdPEDF, or an empty vector (AdNull). Endpoints measured included transgene expression, tumor size, and animal survival, as well as microvessel density within the tumor. Additionally, a murine pulmonary metastasis model was established by intravenous injection of a syngeneic colon adenocarcinoma cell line expressing a marker gene (beta-galactosidase). One day later, treatment (phosphate-buffered saline, AdNull, or AdPEDF) was administered intrapleurally. Tumor burden (gross and histologic inspection, lung weight, and beta-galactosidase expression) was then evaluated 13 days after vector dosing, and survival was recorded. AdPEDF-derived expression of pigment epithelium-derived factor was demonstrated in vitro and in vivo. In syngeneic murine lung cancer flank tumors, intratumoral administration of AdPEDF significantly inhibited tumor growth (P <.01), prolonged mouse survival (P <.01), and decreased microvessel density (P <.01) compared with control groups. In the pulmonary metastasis model, AdPEDF-treated mice exhibited significantly reduced lung lesions, lung weight (P <.0005), beta-galactosidase expression (P <.05), and animal survival was prolonged (P <.05). Gene transfer of pigment epithelium-derived factor suppresses tumor vascularization and growth, while prolonging survival in syngeneic murine models of thoracic malignancies.

publication date

  • July 2003

has subject area

  • Adenoviruses, Human
  • Animals
  • Carcinoma, Squamous Cell
  • Disease Models, Animal
  • Eye Proteins
  • Female
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors
  • Injections, Intravenous
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Models, Cardiovascular
  • Nerve Growth Factors
  • Protein Biosynthesis
  • Proteins
  • Serpins
  • Survival Analysis
  • Thoracic Neoplasms
  • Tumor Cells, Cultured

Research

keywords

  • Comparative Study
  • Evaluation Studies
  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 12878936

Additional Document Info

start page

  • 28

end page

  • 38

volume

  • 126

number

  • 1