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Citation
Tags
HERO ID
7427103
Reference Type
Journal Article
Title
An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line
Author(s)
Wang, Y; Xue, H; Cutz, JC; Bayani, J; Mawji, NR; Chen, WG; Goetz, LJ; Hayward, SW; Sadar, MD; Gilks, CB; Gout, PW; Squire, JA; Cunha, GR; Wang, YZ; ,
Year
2005
Is Peer Reviewed?
1
Journal
Laboratory Investigation
ISSN:
0023-6837
EISSN:
1530-0307
Publisher
NATURE PUBLISHING GROUP
Location
NEW YORK
Page Numbers
1392-1404
Language
English
PMID
16155594
DOI
10.1038/labinvest.3700335
Web of Science Id
WOS:000232807600008
URL
http://www.nature.com/articles/3700335
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Abstract
Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.
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