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Endocr Pathol. 2016 Jun;27(2):97-103. doi: 10.1007/s12022-016-9429-4.

Establishment and Characterization of a Human Neuroendocrine Tumor Xenograft.

Yang Z1,2, Zhang L1,2, Serra S2,3, Law C4,5, Wei A2,5, Stockley TL2,3, Ezzat S2,6, Asa SL7,8,9.

Author information

1
Department of Breast Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, 130033, People's Republic of China.
2
Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
4
Department of Surgery and Odette Cancer Centre, Sunnybrook Hospital, Toronto, Ontario, Canada.
5
Department of Surgery, University of Toronto, Toronto, Canada.
6
Department of Medicine, University of Toronto, Toronto, Canada.
7
Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada. sylvia.asa@uhn.ca.
8
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. sylvia.asa@uhn.ca.
9
Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, Ontario, M5G 2S3, Canada. sylvia.asa@uhn.ca.

Abstract

Neuroendocrine tumors (NETs) are increasing in incidence yet the cause of these tumors remains unknown. Familial associations have shed light on the genetic basis of some of these tumors, but sporadic tumors seem to have primarily epigenetic dysregulation. The rarity of cell lines and animal models has been a barrier to studies of treatment modalities. We set out to develop a xenograft model of gastrointestinal NETs. Primary human NETs were collected at the time of surgery under sterile conditions and xenografted into the flanks of immunodeficient mice. Tumor growth was measured and when tumors reached 1500 mm(3), they were excised and half was re-xenografted through multiple generations. The other half was bisected; a part was frozen and a part was fixed for morphologic and immunohistochemical characterization as well as molecular validation of fidelity of a successful xenograft. Of 106 human NETs, seven were successfully engrafted of which only one tumor was successfully propagated for eight passages. Two years later, the tumor retains its neuroendocrine features and similarity to the original primary human tumor. It has retained expression of keratin as well as chromogranin A reactivity. The establishment of a NET xenograft provides a model for further study of the biological behavior of these tumors and can be used to examine the in vivo effects of various medical and targeted radiotherapeutic agents on tumor growth.

KEYWORDS:

Cell lines; Mouse model; Neuroendocrine tumor; Xenograft

PMID:
27067082
DOI:
10.1007/s12022-016-9429-4
[Indexed for MEDLINE]

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