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


CONCLUSIONS
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.
Flatmark
Kjersti
K
Department of Surgical Oncology, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, Oslo, Norway. kjersti.flatmark@rr-research.no
Reed
Wenche
W
Halvorsen
Thomas
T
Sørensen
Olaf
O
Wiig
Johan N
JN
Larsen
Stein G
SG
Fodstad
Øystein
Ø
Giercksky
Karl-Erik
KE
D000369:Aged, 80 and over; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053554:Keratin-20 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology*; D011553:Pseudomyxoma Peritonei / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D013997:Time Factors; D014183:Transplantation, Heterologous
D002272:Carcinoembryonic Antigen; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; D019394:Ki-67 Antigen; D009077:Mucins