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

Stoeltzing O, Ahmad SA, Liu W, McCarty MF, Parikh AA, Fan F, Reinmuth N, Bucana CD, Ellis LM
Br J Cancer. 2002 87 (10): 1182-7

PMID: 12402160 · PMCID: PMC2376191 · 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.

MeSH Terms (21)

Angiogenesis Inducing Agents Angiogenesis Inhibitors Angiopoietin-1 Animals Ascites Capillary Permeability Cell Division Colonic Neoplasms Endothelial Growth Factors Humans Intercellular Signaling Peptides and Proteins Lymphokines Male Membrane Glycoproteins Mice Mice, Nude Neovascularization, Pathologic Peritoneal Neoplasms Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors

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