Research article

Pseudomyxoma peritonei – two novel orthotopic mouse models portray the PMCA-I histopathologic subtype

Kjersti Flatmark^1,2,4 , Wenche Reed³ , Thomas Halvorsen² , Olaf Sørensen¹ , Johan N Wiig¹ , Stein G Larsen¹ , Øystein Fodstad^2,4 and Karl-Erik Giercksky^1,4

¹Department of Surgical Oncology, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, 0310 Oslo, Norway

²Department of Tumor Biology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, 0310 Oslo, Norway

³Department of Pathology, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, 0310 Oslo, Norway

⁴Norwegian Radium Hospital Faculty Division, University of Oslo, 0310 Oslo, Norway

author email corresponding author email

BMC Cancer 2007, 7:116doi:10.1186/1471-2407-7-116

Published:	30 June 2007

Abstract

Background

Pseudomyxoma peritonei (PMP) is a rare malignant disease, most commonly originating from appendiceal lesions and characterized by accumulation of mucinous tumor tissue in the peritoneal cavity. Since the disease is infrequent, the task of carrying out studies of treatment efficacy and disease biology in the clinical setting is challenging, warranting the development of relevant in vitro and in vivo PMP models.

Methods

Human tumor tissue was implanted in the peritoneal cavity of nude mice to establish two orthotopic models exhibiting noninvasive intraperitoneal growth without metastasis development.

Results

Xenograft tissues have retained essential properties of the original human tumors, such as macro- and microscopic growth patterns, mucin production as well as expression of carcinoembryonal antigen, cytokeratins 20 and 7 and the proliferation marker pKi67. Upon microscopic examination, the human tumors were categorized as the PMCA-I (peritoneal mucinous carcinomatosis of intermediate features) subtype, which was conserved through 14 examined passages in mice, for the first time modeling this particular histopathologic category.

Conclusion

In conclusion, two novel orthotopic models of human PMP have been established that consistently portray a distinct histopathologic subtype and reflect essential human tumor properties. Xenografts can easily and reproducibly be transferred to new generations of mice with acceptable passage periods, rendering the models as attractive tools for further studies of PMP biology and treatment.