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Research ArticleExperimental Studies

A Novel Orthotopic Mouse Model of Lung Metastasis Using Fluorescent Patient-derived Osteosarcoma Cells

HIROMICHI OSHIRO, YASUNORI TOME, KENTARO MIYAKE, TAKASHI HIGUCHI, NORIHIKO SUGISAWA, JUN HO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, FUMINORI KANAYA, KOTARO NISHIDA and ROBERT M. HOFFMAN
Anticancer Research February 2021, 41 (2) 635-640; DOI: https://doi.org/10.21873/anticanres.14814
HIROMICHI OSHIRO
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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YASUNORI TOME
3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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  • For correspondence: all@anticancer.com yastome@med.u-ryukyu.ac.jp
KENTARO MIYAKE
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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TAKASHI HIGUCHI
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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NORIHIKO SUGISAWA
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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JUN HO PARK
1AntiCancer Inc., San Diego, CA, U.S.A.;
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ZHIYING ZHANG
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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SAHAR RAZMJOOEI
1AntiCancer Inc., San Diego, CA, U.S.A.;
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FUMINORI KANAYA
3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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KOTARO NISHIDA
3Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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ROBERT M. HOFFMAN
1AntiCancer Inc., San Diego, CA, U.S.A.;
2Department of Surgery, University of California, San Diego, CA, U.S.A.;
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  • For correspondence: all@anticancer.com yastome@med.u-ryukyu.ac.jp
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Abstract

Background: A mouse model of metastatic osteosarcoma is imperative to identify effective agents for metastatic osteosarcoma, which is a recalcitrant disease. In the present study, we established osteosarcoma patient-derived cells (OS-PDCs) and transfected them with green fluorescent protein (GFP). Materials and Methods: The OS-PDCs were transfected with GFP-lentivirus. GFP-expressing OS-PDCs (2.0×105) were then injected into the tibia of nude mice to establish the patient-derived orthotopic cell (PDOC) model (n=3). Six weeks after injection, the primary tumor and each organ were resected and imaged. Results: Primary orthotopic tumors were established in two out of three mice. The GFP-expressing OS-PDCs in the PDOC model were visualized. Multiple GFP-expressing lung metastases were detected in one of the two mice with primary tumor. Conclusion: The present study proves the concept that a GFP-expressing PDOC model can mimic clinical lung-metastatic osteosarcoma. This model can serve as a paradigm to screen for effective drugs for osteosarcoma lung metastasis.

Key Words:
  • Osteosarcoma
  • metastasis
  • patient-derived orthotopic xenograft
  • PDOX
  • patient-derived cells
  • PDC
  • lung metastasis
  • green fluorescent protein
  • imaging
  • Received December 5, 2020.
  • Revision received December 20, 2020.
  • Accepted December 23, 2020.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (2)
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A Novel Orthotopic Mouse Model of Lung Metastasis Using Fluorescent Patient-derived Osteosarcoma Cells
HIROMICHI OSHIRO, YASUNORI TOME, KENTARO MIYAKE, TAKASHI HIGUCHI, NORIHIKO SUGISAWA, JUN HO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, FUMINORI KANAYA, KOTARO NISHIDA, ROBERT M. HOFFMAN
Anticancer Research Feb 2021, 41 (2) 635-640; DOI: 10.21873/anticanres.14814

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A Novel Orthotopic Mouse Model of Lung Metastasis Using Fluorescent Patient-derived Osteosarcoma Cells
HIROMICHI OSHIRO, YASUNORI TOME, KENTARO MIYAKE, TAKASHI HIGUCHI, NORIHIKO SUGISAWA, JUN HO PARK, ZHIYING ZHANG, SAHAR RAZMJOOEI, FUMINORI KANAYA, KOTARO NISHIDA, ROBERT M. HOFFMAN
Anticancer Research Feb 2021, 41 (2) 635-640; DOI: 10.21873/anticanres.14814
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Keywords

  • Osteosarcoma
  • Metastasis
  • patient-derived orthotopic xenograft
  • PDOX
  • patient-derived cells
  • PDC
  • lung metastasis
  • green fluorescent protein
  • imaging
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