Development and characterization of a novel in vivo model of carcinoid syndrome.
OBJECTIVE
Carcinoid syndrome, characterized by flushing, diarrhea, and valvular heart disease, can occur following carcinoid tumor metastasis to the liver and systemic release of bioactive hormones into the systemic circulation. Treatment of this devastating disease is hampered by the lack of an in vivo model that recapitulates the clinical syndrome.


METHODS
Here, we have injected BON cells, a novel human carcinoid cell line established in our laboratory, into the spleens of athymic nude mice to establish liver metastases.


RESULTS
The majority of mice injected intrasplenically with BON cells developed significant increases in plasma serotonin and urine 5-hydroxyindoleacetic acid, and several mice exhibited mesenteric fibrosis, diarrhea, and fibrotic cardiac valvular disease reminiscent of carcinoid syndrome by both echocardiographic and histopathologic evaluation. Mice pretreated with octreotide, a long-acting somatostatin analogue, or bevacizumab, a vascular endothelial growth factor inhibitor, developed fewer liver metastases and manifestations of carcinoid syndrome, including valvular heart disease.


CONCLUSIONS
We have provided an important in vivo model to further delineate novel treatment modalities for carcinoid syndrome that will also be useful to elucidate the factors contributing to the sequelae of carcinoid disease (e.g., mesenteric fibrosis and valvular heart disease).
Jackson
Lindsey N
LN
Department of Surgery and Pathology, The University of Texas Medical Branch, Galveston, Texas 77555-0536, USA.
Chen
L Andy
LA
Larson
Shawn D
SD
Silva
Scott R
SR
Rychahou
Piotr G
PG
Boor
Paul J
PJ
Li
Jing
J
Defreitas
Gilberto
G
Stafford
W Lane
WL
Townsend
Courtney M
CM
Evers
B Mark
BM