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 Townsend, B. Mark Evers

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

Fingerprint

Carcinoid Tumor
Heart Valve Diseases
Neoplasm Metastasis
Nude Mice
Diarrhea
Liver
Fibrosis
Hydroxyindoleacetic Acid
Octreotide
Somatostatin
Vascular Endothelial Growth Factor A
Heart Diseases
Serotonin
Research Design
Spleen
Urine
Hormones
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jackson, L. N., Chen, L. A., Larson, S. D., Silva, S. R., Rychahou, P. G., Boor, P., ... 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

Development and characterization of a novel in vivo model of carcinoid syndrome. / Jackson, Lindsey N.; Chen, L. Andy; Larson, Shawn D.; Silva, Scott R.; Rychahou, Piotr G.; Boor, Paulj; Li, Jing; Defreitas, Gilberto; Stafford, W. Lane; Townsend, Courtney; Evers, B. Mark.

In: Clinical Cancer Research, Vol. 15, No. 8, 15.04.2009, p. 2747-2755.

Research output: Contribution to journalArticle

Jackson, LN, Chen, LA, Larson, SD, Silva, SR, Rychahou, PG, Boor, P, Li, J, Defreitas, G, Stafford, WL, Townsend, C & Evers, BM 2009, 'Development and characterization of a novel in vivo model of carcinoid syndrome', Clinical Cancer Research, vol. 15, no. 8, pp. 2747-2755. https://doi.org/10.1158/1078-0432.CCR-08-2346
Jackson LN, Chen LA, Larson SD, Silva SR, Rychahou PG, Boor P et al. Development and characterization of a novel in vivo model of carcinoid syndrome. Clinical Cancer Research. 2009 Apr 15;15(8):2747-2755. https://doi.org/10.1158/1078-0432.CCR-08-2346
Jackson, Lindsey N. ; Chen, L. Andy ; Larson, Shawn D. ; Silva, Scott R. ; Rychahou, Piotr G. ; Boor, Paulj ; Li, Jing ; Defreitas, Gilberto ; Stafford, W. Lane ; Townsend, Courtney ; Evers, B. Mark. / Development and characterization of a novel in vivo model of carcinoid syndrome. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 8. pp. 2747-2755.
@article{77be6b8c750d42dda85b5255f18a7221,
title = "Development and characterization of a novel in vivo model of carcinoid syndrome",
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).",
author = "Jackson, {Lindsey N.} and Chen, {L. Andy} and Larson, {Shawn D.} and Silva, {Scott R.} and Rychahou, {Piotr G.} and Paulj Boor and Jing Li and Gilberto Defreitas and Stafford, {W. Lane} and Courtney Townsend and Evers, {B. Mark}",
year = "2009",
month = "4",
day = "15",
doi = "10.1158/1078-0432.CCR-08-2346",
language = "English (US)",
volume = "15",
pages = "2747--2755",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

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

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

UR - http://www.scopus.com/inward/citedby.url?scp=65249097215&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-2346

DO - 10.1158/1078-0432.CCR-08-2346

M3 - Article

VL - 15

SP - 2747

EP - 2755

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 8

ER -