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A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate.

Authors
  • Ishiyama, Shun1
  • Kissel, Casey2
  • Guo, Xin3
  • Howard, Alexis4
  • Saeki, Harumi5
  • Ito, Tomoaki6
  • Sysa-Shah, Polina7
  • Orita, Hajime8
  • Sakamoto, Kazuhiro9
  • Gabrielson, Kathleen10
  • 1 Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University; Department of Surgery, Johns Hopkins University School of Medicine; Department of Coloproctological Surgery, Juntendo University Faculty of Medicine.
  • 2 Program for Comparative Medicine, Gene Therapy Program, Perelman School of Medicine, University of Pennsylvania.
  • 3 Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine.
  • 4 Tuskegee College of Veterinary Medicine.
  • 5 Department of Human Pathology, Juntendo University Faculty of Medicine.
  • 6 Department of Surgery, Juntendo University Shizuoka Hospital, Juntendo University School of Medicine.
  • 7 Department of Urology, The Johns Hopkins School of Medicine.
  • 8 Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Faculty of Medicine.
  • 9 Department of Coloproctological Surgery, Juntendo University Faculty of Medicine.
  • 10 Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University; [email protected]
Type
Published Article
Journal
Journal of Visualized Experiments
Publisher
MyJoVE Corporation
Publication Date
May 03, 2021
Issue
171
Identifiers
DOI: 10.3791/62139
PMID: 33999035
Source
Medline
Language
English
License
Unknown

Abstract

The most recent advance in the treatment of osteosarcoma (OS) occurred in the 1980s when multi-agent chemotherapy was shown to improve overall survival compared to surgery alone. To address this problem, the aim of the study is to refine a lesser-known model of OS in rats with a comprehensive histologic, imaging, biologic, implantation, and amputation surgical approach that prolongs survival. We used an immunocompetent, outbred Sprague-Dawley (SD), syngeneic rat model with implanted UMR106 OS cell line (originating from a SD rat) with orthotopic tibial tumor implants into 3-week-old male and female rats to model pediatric OS. We found that rats develop reproducible primary and metastatic pulmonary tumors, and that limb amputations at 3 weeks post implantation significantly reduce the incidence of pulmonary metastasis and prevent unexpected deaths. Histologically, the primary and metastatic OSs in rats were very similar to human OS. Using immunohistochemistry methods, the study shows that rat OS are infiltrated with macrophages and T cells. A protein expression survey of OS cells reveals that these tumors express ErbB family kinases. Since these kinases are also highly expressed in most human OSs, this rat model could be used to test ErbB pathway inhibitors for therapy.

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