title: Pancreatic cancer growth is inhibited by blockade of VEGF-RII.
abstract: BACKGROUND
  Angiogenesis is important in the development and progression of pancreatic cancer. Therefore antiangiogenic therapy targeting endothelial cells may represent a promising therapeutic option. The aim of the study was to evaluate antiangiogenic therapy as a potential therapeutic option in pancreatic cancer.
  
  
  METHODS
  Replication-deficient retroviruses encoding truncated VEGF-RII were used to block vascular endothelial growth factor (VEGF) signaling. Tumor growth of 3 pancreatic cancer cell lines was assayed in a nude mouse model in which each pancreatic cancer cell line was subcutaneously inoculated together with retrovirus-producing cells. Expression of VEGF was assayed by RT-PCR and by enzyme-linked immunosorbent assay. Oxygen tension in tumors was determined polarographically.
  
  
  RESULTS
  All 3 pancreatic cancer cell lines expressed VEGF mRNA, with the highest VEGF secretion seen in MIA PaCa-2 cells. In vivo therapeutic intervention through dominant negative inhibition of VEGF-RII significantly reduced the growth rate of subcutaneous tumors and inhibited tumor neoangiogenesis. Tumor oxygenation, however, was not altered in xenograft tumors treated with dominant negative retroviruses.
  
  
  CONCLUSIONS
  The ligand/receptor system consisting of VEGF and VEGF-RII seems to be of biologic significance in the pathogenesis of pancreatic cancer growth. Therefore therapeutic intervention in this angiogenic system by a retroviral-based gene transfer technology represents a rational and feasible new technique to inhibit tumor growth.
authors.affiliation: Department of Surgery, UCLA School of Medicine, University of California-Los Angeles, 10833 Le Conte, Los Angeles, CA 90095-6904, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Büchler
authors.forename: Howard A
authors.initials: HA
authors.lastname: Reber
authors.forename: Axel
authors.initials: A
authors.lastname: Ullrich
authors.forename: Mark
authors.initials: M
authors.lastname: Shiroiki
authors.forename: Mendel
authors.initials: M
authors.lastname: Roth
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lavey
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Oscar J
authors.initials: OJ
authors.lastname: Hines
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D012190:Retroviridae / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2