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Effects of primary and recurrent sacral chordoma on the motor and nociceptive function of hindlimbs in rats: an orthotopic spine model.
- Source :
-
Journal of neurosurgery. Spine [J Neurosurg Spine] 2017 Aug; Vol. 27 (2), pp. 215-226. Date of Electronic Publication: 2017 Jun 09. - Publication Year :
- 2017
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Abstract
- OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.
- Subjects :
- Animals
Cell Line, Tumor
Chordoma diagnostic imaging
Chordoma pathology
Female
Gait physiology
Humans
Immunocompromised Host
Neoplasm Recurrence, Local physiopathology
Neoplasm Transplantation
Random Allocation
Rats
Sacrum
Spinal Cord diagnostic imaging
Spinal Cord pathology
Spinal Cord physiopathology
Spinal Neoplasms diagnostic imaging
Spinal Neoplasms pathology
Chordoma physiopathology
Disease Models, Animal
Hindlimb physiopathology
Motor Activity physiology
Nociception physiology
Spinal Neoplasms physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1547-5646
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of neurosurgery. Spine
- Publication Type :
- Academic Journal
- Accession number :
- 28598292
- Full Text :
- https://doi.org/10.3171/2016.12.SPINE16917