Development and characterization of a novel in vivo model of carcinoid syndrome

Lindsey N. Jackson, L. Andy Chen, Shawn D. Larson, Scott R. Silva, Piotr G. Rychahou, Paulj Boor, Jing Li, Gilberto Defreitas, W. Lane Stafford, Courtney M. Townsend, B. Mark Evers

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)2747-2755
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number8
DOIs
StatePublished - Apr 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jackson, L. N., Chen, L. A., Larson, S. D., Silva, S. R., Rychahou, P. G., Boor, P., Li, J., Defreitas, G., Stafford, W. L., Townsend, C. M., & Evers, B. M. (2009). Development and characterization of a novel in vivo model of carcinoid syndrome. Clinical Cancer Research, 15(8), 2747-2755. https://doi.org/10.1158/1078-0432.CCR-08-2346