TY - JOUR
T1 - Development and characterization of a novel in vivo model of carcinoid syndrome
AU - Jackson, Lindsey N.
AU - Chen, L. Andy
AU - Larson, Shawn D.
AU - Silva, Scott R.
AU - Rychahou, Piotr G.
AU - Boor, Paulj
AU - Li, Jing
AU - Defreitas, Gilberto
AU - Stafford, W. Lane
AU - Townsend, Courtney M.
AU - Evers, B. Mark
PY - 2009/4/15
Y1 - 2009/4/15
N2 - Purpose: 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. Experimental Design: 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. Conclusion: 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).
AB - Purpose: 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. Experimental Design: 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. Conclusion: 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).
UR - http://www.scopus.com/inward/record.url?scp=65249097215&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-2346
DO - 10.1158/1078-0432.CCR-08-2346
M3 - Article
C2 - 19336516
AN - SCOPUS:65249097215
SN - 1078-0432
VL - 15
SP - 2747
EP - 2755
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -