Angiopoietin-1 inhibits tumour growth and ascites formation in a murine model of peritoneal carcinomatosis

Br J Cancer. 2002 Nov 4;87(10):1182-7. doi: 10.1038/sj.bjc.6600598.


Angiopoietin-1 is an important regulator of endothelial cell survival. Angiopoietin-1 also reduces vascular permeability mediated by vascular endothelial growth factor. The effects of angiopoietin-1 on tumour growth and angiogenesis are controversial. We hypothesised that angiopoietin-1 would decrease tumour growth and ascites formation in peritoneal carcinomatosis. Human colon cancer cells (KM12L4) were transfected with vector (pcDNA) alone (control) or vector containing angiopoietin-1 and injected into the peritoneal cavities of mice. After 30 days, the following parameters were measured: number of peritoneal nodules, ascites volume, and diameter of the largest tumour. Effects of angiopoietin-1 on vascular permeability were investigated using an intradermal Miles assay with conditioned media from transfected cells. Seven of the nine mice in the pcDNA group developed ascites (1.3+/-0.5 ml (mean+/-s.e.m.)), whereas no ascites was detectable in the angiopoietin-1 group (0 out of 10) (P<0.01). Number of peritoneal metastases (P<0.05), tumour volume, (P<0.05), vessel counts (P<0.01), and tumour cell proliferation (P<0.01) were significantly reduced in angiopoietin-1-expressing tumours. Conditioned medium from angiopoietin-1-transfected cells decreased vascular permeability more than did conditioned medium from control cells (P<0.05). Our results suggest that angiopoietin-1 is an important mediator of angiogenesis and vascular permeability and thus could theoretically serve as an anti-neoplastic agent for patients with carcinomatosis from colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inducing Agents / physiology*
  • Angiogenesis Inhibitors / therapeutic use
  • Angiopoietin-1
  • Animals
  • Ascites / prevention & control*
  • Capillary Permeability
  • Cell Division
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Endothelial Growth Factors / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology
  • Lymphokines / physiology
  • Male
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control*
  • Peritoneal Neoplasms / blood supply
  • Peritoneal Neoplasms / secondary*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • ANGPT1 protein, human
  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Membrane Glycoproteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors