Inhibition of colon cancer metastasis by a 3'- end antisense urokinase receptor mRNA in a nude mouse model

Int J Cancer. 2001 Apr 15;92(2):257-62. doi: 10.1002/1097-0215(200102)9999:9999<::aid-ijc1178>;2-6.


The role of urokinase-type plasminogen activator receptor (uPAR) in human colon cancer metastasis has not been tested using an antisense approach. In our study, the HCT116 cells, with high metastatic potential were transfected with expression vectors containing a 3' or 5' uPAR cDNA fragment in an antisense (AS) orientation. Transfection of 4 clones was confirmed by DNA hybridization analysis. Receptor-bound endogenous uPA activities of the clones were reduced to 16-68% of controls. The extracellular matrix degradation by the 4 clones was decreased to 33-76%. Two of the clones, 3'-AS7 and 5'-AS, were evaluated in an in vivo assay system of experimental metastasis using athymic mice. Pulmonary metastases were found in 63-78% mice injected with the parent HCT116 or control cells. In mice injected intravenously with the antisense transfected clones, 3'-AS7 and 5'-AS, however, pulmonary metastases were found in only 19% and 9% respectively (p < 0.05). These results provide direct evidence that both 3' and 5'-AS uPAR can inhibit colon cancer invasion and metastasis and may offer the prospect of defining specific targets for gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clone Cells
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / prevention & control*
  • DNA, Complementary
  • Extracellular Matrix / metabolism
  • Humans
  • Injections, Intravenous
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • RNA, Antisense / genetics*
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Transfection
  • Tumor Cells, Cultured


  • DNA, Complementary
  • PLAUR protein, human
  • Plaur protein, mouse
  • RNA, Antisense
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator