Orthotopic animal model of pseudomyxoma peritonei: An in vivo model to test anti-angiogenic drug effects

Anthony Dohan; Ruben Lousquy; Clarisse Eveno; Diane Goere; Dong Broqueres-You; Rachid Kaci; Jacqueline Lehmann-Che; Jean-Marie Launay; Philippe Soyer; Philippe Bonnin; Marc Pocard

doi:10.1016/j.ajpath.2014.03.004

Orthotopic animal model of pseudomyxoma peritonei: An in vivo model to test anti-angiogenic drug effects

Am J Pathol. 2014 Jul;184(7):1920-9. doi: 10.1016/j.ajpath.2014.03.004. Epub 2014 May 9.

Authors

Affiliations

¹ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Department of Body and Interventional Imaging, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Paris, France. Electronic address: anthony.dohan@lrb.aphp.fr.
² INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France.
³ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Surgical Oncologic and Digestive Unit, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France.
⁴ Department of Surgical Oncology, Gustave Roussy Institute, Villejuif, France.
⁵ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Blood and Vessels Institute, Paris Diderot University, Sorbonne Paris Cité, Lariboisière Hospital, Paris, France.
⁶ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Department of Pathology, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France.
⁷ Department of Biochemistry and INSERM U944, Paris Diderot University, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Saint-Louis Hospital, Paris, France.
⁸ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Department of Biochemistry, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France.
⁹ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Department of Body and Interventional Imaging, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹⁰ INSERM U965, C.A.R.T. Carcinomatosis Angiogenesis and Translational Research, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France; Department of Clinical Physiology-Functional Investigations, Lariboisière Hospital, Paris Diderot University, Sorbonne Paris Cité, AP-HP, Paris, France.

PMID: 24814606
DOI: 10.1016/j.ajpath.2014.03.004

Abstract

Pseudomyxoma peritonei (PMP) is an uncommon peritoneal mucinous carcinomatosis confined to the peritoneal cavity. The rarity of PMP in humans makes evaluation of the disease biological features and new therapeutic strategies difficult. Accordingly, there is a need for animal models of PMP. Human PMP tissue was i.p. grafted and grown into nude mice, then constituted into reliable and reproducible orthotopic models. Histological and immunostaining analysis was performed. Bevacizumab was injected twice a week either during tumor growth or after cytoreductive surgery. In vivo imaging of tumor angiogenesis was performed using barium sulfate or isolectin microangiography and Doppler ultrasonography of the superior mesenteric artery. Tumor angiogenesis was confirmed by the presence of tortuous vascular networks with high levels of expression of CD31, vascular endothelial cadherin, and desmin. Doppler ultrasonography of the superior mesenteric artery revealed a twofold increase in blood flow velocity compared with tumor-free mice (P < 0.001). Bevacizumab administration was correlated with the normalization of tumor vascularity when injected during tumor growth and with the stabilization of the histological and hemodynamic findings when injected after cytoreductive surgery. Our PMP models mimic human PMP. Our results confirmed the presence of tumor angiogenesis related to PMP growth. Our murine model allows researchers to actually bench test and evaluate, in preclinical studies, the efficacy of new therapeutic strategies and anti-angiogenic therapies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / therapeutic use*
Animals
Antibodies, Monoclonal, Humanized / therapeutic use
Bevacizumab
Blood Flow Velocity
Disease Models, Animal*
Female
Humans
Mesenteric Arteries / diagnostic imaging
Mice, Nude
Neovascularization, Pathologic / drug therapy
Peritoneal Neoplasms / drug therapy*
Pseudomyxoma Peritonei / drug therapy*
Ultrasonography

Substances

Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Bevacizumab