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Real‐time whole‐body imaging of an orthotopic metastatic prostate cancer model expressing red fluorescent protein
Author(s) -
Yang Meng,
Jiang Ping,
Yamamoto Norio,
Li Lingna,
Geller Jack,
Moossa A. R.,
Hoffman Robert M.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20125
Subject(s) - prostate cancer , metastasis , medicine , pathology , lymphatic system , prostate , primary tumor , lymph node , cancer , cancer research
Abstract Background We describe here, a whole‐body imageable spontaneous metastatic model of human prostate cancer developed by surgical orthotopic implantation (SOI) and visualized by red fluorescent protein (RFP) expression. Methods Human prostate cancer PC‐3 cells were transduced with the pLNCX2‐DsRed‐2‐RFP retroviral vector containing the RFP and neomycin‐resistance genes. A stable RFP‐expressing PC‐3 clone was selected in 800 μg/ml G418 in vitro and injected subcutaneously in nude mice. Stable high‐level expression of RFP was maintained in the subcutaneously‐growing tumors. To utilize RFP expression for metastasis studies, fragments of the subcutaneously‐growing tumor, which were comprised of RFP‐expressing cells, were implanted by SOI in the prostate of nude mice. Results Primary tumor growth, progression, and subsequent lymphatic metastases were visualized in live, intact animals in real time by whole‐body RFP fluorescence imaging. In total, 100% of the experimental animals developed lymphatic metastasis, the growth of which was monitored in real time by whole‐body imaging. The aggressive lymphatic metastasis in this model reflects one of the major metastatic routes of prostate cancer in human patients. Intravital RFP imaging visualized single cancer cells in the lung and bladder. Open RFP imaging at autopsy visualized extensive primary growth and highly disseminated lymph‐node metastases. Conclusions The long‐wavelength emission of RFP enabled high sensitivity and resolution of microscopic tumor growth using appropriate imaging techniques. The model should be useful for the real‐time evaluation of novel therapeutics for metastatic prostate cancer. © 2004 Wiley‐Liss, Inc.