Targeting the urokinase plasminogen activator receptor with a monoclonal antibody impairs the growth of human colorectal cancer in the liver

Cancer. 2009 Jul 15;115(14):3360-8. doi: 10.1002/cncr.24371.


Background: Urokinase plasminogen activator receptor (uPAR) expression has been shown to correlate with poor prognosis in colorectal cancer (CRC). The authors hypothesized that targeting uPAR, a receptor involved in cell proliferation, migration, invasion, adhesion, and angiogenesis, would impair the growth of CRC in the liver, the most common site of metastasis.

Methods: Human CRC cell lines were examined for uPAR expression by Western blot analysis. The in vitro effects of the uPAR monoclonal antibody (MoAb) (ATN-658) were tested in proliferation and migration assays. For in vivo studies, human HCT116 CRC cells were injected directly into the livers of mice in 2 separate studies, the first to determine the effect of therapy with ATN-658 on small-volume disease (therapy begun on Day 4), and a second study to determine the effect of therapy on established disease (therapy begun on Day 12). Mice were randomized to receive either nonspecific immunoglobulin G MoAb (control) or ATN-658, and were sacrificed 1 month after tumor implantation.

Results: uPAR was expressed by all CRC cell lines studied. In vitro, ATN-658 had minimal effect on CRC proliferation in monolayers, but significantly decreased CRC cell migration. In vivo, ATN-658 lead to significant reductions in tumor growth versus control when initiated either 4 or 12 days after tumor implantation (-65% vs control [P < or = .05] and -85% vs control [P < or = .05]). ATN-658 significantly inhibited in vivo tumor cell proliferation in both studies.

Conclusions: uPAR MoAb therapy impaired CRC tumor growth in the liver in both small-volume and large-volume disease models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / pathology*
  • Humans
  • Liver Neoplasms, Experimental / prevention & control
  • Liver Neoplasms, Experimental / secondary*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Random Allocation
  • Receptors, Urokinase Plasminogen Activator / immunology*
  • Xenograft Model Antitumor Assays


  • ATN-658
  • Antibodies, Monoclonal
  • Receptors, Urokinase Plasminogen Activator