TY - JOUR
T1 - A rat model of metastatic spinal cord compression using human prostate adenocarcinoma
T2 - Histopathological and functional analysis
AU - Sarabia-Estrada, Rachel
AU - Zadnik, Patricia L.
AU - Molina, Camilo A.
AU - Jimenez-Estrada, Ismael
AU - Groves, Mari L.
AU - Gokaslan, Ziya L.
AU - Bydon, Ali
AU - Witham, Timothy F.
AU - Wolinsky, Jean Paul
AU - Sciubba, Daniel M.
N1 - Funding Information:
Author disclosures: RS-E: Nothing to disclose. PLZ: Nothing to disclose. CAM: Nothing to disclose. IJ-E: Nothing to disclose. MLG: Nothing to disclose. ZLG: Stock Ownership: US Spine (C), Spinal Kinetics (C); Board of Directors: JNS Spine (C), Spine Journal, Journal of Spinal Disorders (C), European Spine Journal (C), Nature Reviews (C), World Neurosurgery (C), Journal of Surgical Oncology (C), US Spine (C); Scientific Advisory Board: NREF (C); Research Support: AO Spine (C), NREF (C); Grants: DePuy (C); Fellowship Support: AO Spine (C), NREF (C). AB: Research Support: Johnson & Johnson (E, Paid directly to institution/employer. TFW: Eli Lilly (unknown, Paid directly to institution/employer). J-PW: Nothing to disclose. DMS: Speaking/Teaching Arrangements: Globus (B, Paid directly to institution/employer), DePuy (B, Paid directly to institution/employer); Grants: DePuy (F, Paid directly to institution/employer).
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/11
Y1 - 2013/11
N2 - Background context: Cancer is a major global public health problem responsible for one in every four deaths in the United States. Prostate cancer alone accounts for 29% of all cancers in men and is the sixth leading cause of death in men. It is estimated that up to 30% of patients with cancer will develop metastatic disease, the spine being one of the most frequently affected sites in patients with prostate cancer. Purpose: To study this condition in a preclinical setting, we have created a novel animal model of human metastatic prostate cancer to the spine and have characterized it histologically, functionally, and via bioluminescence imaging. Study design: Translational science investigation of animal model of human prostate cancer in the spine. Methods: Luciferase-positive human prostate tumor cells PC3 (PC3-Luc) were injected in the flank of athymic male rats. PC3-Luc tumor samples were then implanted into the L5 vertebral body of male athymic rats (5 weeks old). Thirty-two rats were randomized into three surgical groups: experimental, control, and sham. Tumor growth was assessed qualitatively and noninvasively via bioluminescence emission, upon luciferin injection. To determine the functional impact of tumor growth in the spine, rats were evaluated for gait abnormalities during gait locomotion using video-assisted gait analysis. Rats were euthanized 22 days after tumor implantation, and spines were subjected to histopathological analyses. Results: Twenty days after tumor implantation, the tumor-implanted rats showed distinct signs of gait disturbances: dragging tail, right- or left-hind limb uncoordination, and absence of toe clearance during forward limb movement. At 20 days, all rats experienced tumor growth, evidenced by bioluminescent signal. Locomotion parameters negatively affected in tumor-implanted rats included stride length, velocity, and duration. At necropsy, all spines showed evidence of tumor growth, and the histological analysis found spinal cord compression and peritumoral osteoblastic reaction characteristic of bony prostate tumors. None of the rats in the sham or control groups demonstrated any evidence of bioluminescence signal or signs of gait disturbances. Conclusions: In this project, we have developed a novel animal model of metastatic spine cancer using human prostate cancer cells. Tumor growth, evaluated via bioluminescence and corroborated by histopathological analyses, affected hind limb locomotion in ways that mimic motor deficits present in humans afflicted with metastatic spine disease. Our model represents a reliable method to evaluate the experimental therapeutic approaches of human tumors of the spine in animals. Gait locomotion and bioluminescence analyses can be used as surrogate noninvasive methods to evaluate tumor growth in this model.
AB - Background context: Cancer is a major global public health problem responsible for one in every four deaths in the United States. Prostate cancer alone accounts for 29% of all cancers in men and is the sixth leading cause of death in men. It is estimated that up to 30% of patients with cancer will develop metastatic disease, the spine being one of the most frequently affected sites in patients with prostate cancer. Purpose: To study this condition in a preclinical setting, we have created a novel animal model of human metastatic prostate cancer to the spine and have characterized it histologically, functionally, and via bioluminescence imaging. Study design: Translational science investigation of animal model of human prostate cancer in the spine. Methods: Luciferase-positive human prostate tumor cells PC3 (PC3-Luc) were injected in the flank of athymic male rats. PC3-Luc tumor samples were then implanted into the L5 vertebral body of male athymic rats (5 weeks old). Thirty-two rats were randomized into three surgical groups: experimental, control, and sham. Tumor growth was assessed qualitatively and noninvasively via bioluminescence emission, upon luciferin injection. To determine the functional impact of tumor growth in the spine, rats were evaluated for gait abnormalities during gait locomotion using video-assisted gait analysis. Rats were euthanized 22 days after tumor implantation, and spines were subjected to histopathological analyses. Results: Twenty days after tumor implantation, the tumor-implanted rats showed distinct signs of gait disturbances: dragging tail, right- or left-hind limb uncoordination, and absence of toe clearance during forward limb movement. At 20 days, all rats experienced tumor growth, evidenced by bioluminescent signal. Locomotion parameters negatively affected in tumor-implanted rats included stride length, velocity, and duration. At necropsy, all spines showed evidence of tumor growth, and the histological analysis found spinal cord compression and peritumoral osteoblastic reaction characteristic of bony prostate tumors. None of the rats in the sham or control groups demonstrated any evidence of bioluminescence signal or signs of gait disturbances. Conclusions: In this project, we have developed a novel animal model of metastatic spine cancer using human prostate cancer cells. Tumor growth, evaluated via bioluminescence and corroborated by histopathological analyses, affected hind limb locomotion in ways that mimic motor deficits present in humans afflicted with metastatic spine disease. Our model represents a reliable method to evaluate the experimental therapeutic approaches of human tumors of the spine in animals. Gait locomotion and bioluminescence analyses can be used as surrogate noninvasive methods to evaluate tumor growth in this model.
KW - Animal gait locomotion
KW - Animal model
KW - Metastatic prostate cancer
KW - Spinal metastasis
KW - Spine tumor
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U2 - 10.1016/j.spinee.2013.05.021
DO - 10.1016/j.spinee.2013.05.021
M3 - Article
C2 - 23810458
AN - SCOPUS:84889084857
SN - 1529-9430
VL - 13
SP - 1597
EP - 1606
JO - Spine Journal
JF - Spine Journal
IS - 11
ER -