title: Inhibition of angiogenesis and suppression of colorectal cancer metastatic to the liver using the Sleeping Beauty Transposon System.
abstract: BACKGROUND
  Metastatic colon cancer is one of the leading causes of cancer-related death worldwide, with disease progression and metastatic spread being closely associated with angiogenesis. We investigated whether an antiangiogenic gene transfer approach using the Sleeping Beauty (SB) transposon system could be used to inhibit growth of colorectal tumors metastatic to the liver.
  
  
  RESULTS
  Liver CT26 tumor-bearing mice were hydrodynamically injected with different doses of a plasmid containing a transposon encoding an angiostatin-endostatin fusion gene (Statin AE) along with varying amounts of SB transposase-encoding plasmid. Animals that were injected with a low dose (10 μg) of Statin AE transposon plasmid showed a significant decrease in tumor formation only when co-injected with SB transposase-encoding plasmid, while for animals injected with a higher dose (25 μg) of Statin AE transposon, co-injection of SB transposase-encoding plasmid did not significantly affect tumor load. For animals injected with 10 μg Statin AE transposon plasmid, the number of tumor nodules was inversely proportional to the amount of co-injected SB plasmid. Suppression of metastases was further evident in histological analyses, in which untreated animals showed higher levels of tumor cell proliferation and tumor vascularization than animals treated with low dose transposon plasmid.
  
  
  CONCLUSIONS
  These results demonstrate that hepatic colorectal metastases can be reduced using antiangiogenic transposons, and provide evidence for the importance of the transposition process in mediating suppression of these tumors.
authors.affiliation: Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. belur001@umn.edu
authors.forename: Lalitha R
authors.initials: LR
authors.lastname: Belur
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Podetz-Pedersen
authors.forename: Brent S
authors.initials: BS
authors.lastname: Sorenson
authors.forename: Alice H
authors.initials: AH
authors.lastname: Hsu
authors.forename: Josh B
authors.initials: JB
authors.lastname: Parker
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Saltzman
authors.forename: S
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: R Scott
authors.initials: RS
authors.lastname: McIvor
mesh_terms: D043168:Angiostatins / Q000235:genetics*; D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology*; D043169:Endostatins / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000098:blood supply / Q000556:secondary / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014183:Transplantation, Heterologous; D019895:Transposases / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D043169:Endostatins; D011993:Recombinant Fusion Proteins; D043168:Angiostatins; D019895:Transposases; C494471:sleeping beauty transposase, human