Influence of adenoviral vector on expression of angiogenesis regulating factors in non-small cell lung cancer cell lines.
Gene therapy to suppress the neovascularization of solid tumors may prove to be an effective strategy in cancer therapy. Recombinant adenovirus (Ad) vectors are currently the most widely used vectors for gene transfer. In this study, we examined the expression of angiogenesis-regulating factors in tumor cells infected with the Ad vector. These cells showed upregulation of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) transcription, and a higher protein level of intracellular bFGF and increased VEGF secretion. In addition, we observed an increase of angiostatin-generating activity in the supernatants of infected tumor cells. Supernatants of Ad vector-infected cells did not stimulate endothelial cell proliferation, and inhibited their migration. These results indicate that infection of tumor cells with the Ad vector results in an increase expression of angiogenesis-regulating factors, but does not by itself activate angiogenesis.
Kuhn
Hartmut
H
Department of Medicine I, University of Leipzig, Johannisallee 32, 04103 Leipzig, Germany. kuhnh@medizin.uni-leipzig.de
Riedel
Alexander
A
Eichler
Wolfram
W
Aust
Gabriele
G
Gessner
Christian
C
Wirtz
Hubert
H
D000256:Adenoviridae / Q000235:genetics*; D043168:Angiostatins; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy*; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D008222:Lymphokines / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D043168:Angiostatins; D010958:Plasminogen