TY - JOUR
T1 - Hormone-refractory prostate cancer in the Lobund-Wistar rat
AU - Pollard, Morris
AU - Suckow, Mark A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/9
Y1 - 2005/9
N2 - Research on cancer prevention and therapy must focus on the refractory disease, the fatal end-stage of cancer that develops in patients with organ-related solid tumors. Refractory cancers develop spontaneously in advanced-stage tumors or in relapsed cases after failed therapy. Because neither prevention nor therapy is currently feasible, refractory cancer is a major impediment to survival. There is a great need for an animal model of prostate cancer (PC), one that develops cancer from initial premalignant to the terminal refractory stages. We describe here a model of hormone-refractory prostate cancer (HRPC) that develops spontaneously through two stages by endogenous mechanisms in the Lobund-Wistar (LW) rat. The early premalignant, testosterone (T)-dependent stage is promoted by high levels of endogenous T, and up to age 12 months is reversible by T deprivation; without this intervention, the tumorigenic process progresses to the refractory stage, which is highly aggressive and does not respond to T deprivation or to a wide range of therapies. Initial refractory tumors are palpable at approximately 18 months of age. As they continue to grow, the tumors express characteristics seen in refractory cancers in humans (i.e., hypoxia, expression of hypoxia-inducible factors, and metastasis). Chemically induced HRPCs in LW rats manifest the same two developmental stages, but with shorter latency periods. A transplantable, metastasizing cell line (PAIII) was derived from a germfree LW rat with advanced-stage cancer. Both spontaneous and chemically induced autochthonous HRPC model systems serve as outstanding models for studies on the prevention and therapy of refractory cancer.
AB - Research on cancer prevention and therapy must focus on the refractory disease, the fatal end-stage of cancer that develops in patients with organ-related solid tumors. Refractory cancers develop spontaneously in advanced-stage tumors or in relapsed cases after failed therapy. Because neither prevention nor therapy is currently feasible, refractory cancer is a major impediment to survival. There is a great need for an animal model of prostate cancer (PC), one that develops cancer from initial premalignant to the terminal refractory stages. We describe here a model of hormone-refractory prostate cancer (HRPC) that develops spontaneously through two stages by endogenous mechanisms in the Lobund-Wistar (LW) rat. The early premalignant, testosterone (T)-dependent stage is promoted by high levels of endogenous T, and up to age 12 months is reversible by T deprivation; without this intervention, the tumorigenic process progresses to the refractory stage, which is highly aggressive and does not respond to T deprivation or to a wide range of therapies. Initial refractory tumors are palpable at approximately 18 months of age. As they continue to grow, the tumors express characteristics seen in refractory cancers in humans (i.e., hypoxia, expression of hypoxia-inducible factors, and metastasis). Chemically induced HRPCs in LW rats manifest the same two developmental stages, but with shorter latency periods. A transplantable, metastasizing cell line (PAIII) was derived from a germfree LW rat with advanced-stage cancer. Both spontaneous and chemically induced autochthonous HRPC model systems serve as outstanding models for studies on the prevention and therapy of refractory cancer.
KW - Animal model
KW - Hormone-refractory cancer
KW - Prostate cancer
KW - Rat
KW - Testosterone
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U2 - 10.1177/153537020523000802
DO - 10.1177/153537020523000802
M3 - Short survey
C2 - 16118401
AN - SCOPUS:24144488331
SN - 1535-3702
VL - 230
SP - 520
EP - 526
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 8
ER -