A rat model of metastatic spinal cord compression using human prostate adenocarcinoma: Histopathological and functional analysis

Rachel Sarabia Estrada, Patricia L. Zadnik, Camilo A. Molina, Ismael Jimenez-Estrada, Mari L. Groves, Ziya L. Gokaslan, Ali Bydon, Timothy F. Witham, Jean Paul Wolinsky, Daniel M. Sciubba

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1597-1606
Number of pages10
JournalSpine Journal
Volume13
Issue number11
DOIs
StatePublished - Nov 2013
Externally publishedYes

Fingerprint

Spinal Cord Compression
Prostate
Adenocarcinoma
Neoplasms
Spine
Gait
Locomotion
Prostatic Neoplasms
Growth
Nude Rats
Extremities
Animal Models
Control Groups

Keywords

  • Animal gait locomotion
  • Animal model
  • Metastatic prostate cancer
  • Spinal metastasis
  • Spine tumor

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

A rat model of metastatic spinal cord compression using human prostate adenocarcinoma : Histopathological and functional analysis. / Sarabia Estrada, Rachel; Zadnik, Patricia L.; Molina, Camilo A.; Jimenez-Estrada, Ismael; Groves, Mari L.; Gokaslan, Ziya L.; Bydon, Ali; Witham, Timothy F.; Wolinsky, Jean Paul; Sciubba, Daniel M.

In: Spine Journal, Vol. 13, No. 11, 11.2013, p. 1597-1606.

Research output: Contribution to journalArticle

Sarabia Estrada, R, Zadnik, PL, Molina, CA, Jimenez-Estrada, I, Groves, ML, Gokaslan, ZL, Bydon, A, Witham, TF, Wolinsky, JP & Sciubba, DM 2013, 'A rat model of metastatic spinal cord compression using human prostate adenocarcinoma: Histopathological and functional analysis', Spine Journal, vol. 13, no. 11, pp. 1597-1606. https://doi.org/10.1016/j.spinee.2013.05.021
Sarabia Estrada, Rachel ; Zadnik, Patricia L. ; Molina, Camilo A. ; Jimenez-Estrada, Ismael ; Groves, Mari L. ; Gokaslan, Ziya L. ; Bydon, Ali ; Witham, Timothy F. ; Wolinsky, Jean Paul ; Sciubba, Daniel M. / A rat model of metastatic spinal cord compression using human prostate adenocarcinoma : Histopathological and functional analysis. In: Spine Journal. 2013 ; Vol. 13, No. 11. pp. 1597-1606.
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title = "A rat model of metastatic spinal cord compression using human prostate adenocarcinoma: Histopathological and functional analysis",
abstract = "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.",
keywords = "Animal gait locomotion, Animal model, Metastatic prostate cancer, Spinal metastasis, Spine tumor",
author = "{Sarabia Estrada}, Rachel and Zadnik, {Patricia L.} and Molina, {Camilo A.} and Ismael Jimenez-Estrada and Groves, {Mari L.} and Gokaslan, {Ziya L.} and Ali Bydon and Witham, {Timothy F.} and Wolinsky, {Jean Paul} and Sciubba, {Daniel M.}",
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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.

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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