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

Anticancer Res. 2021 Feb;41(2):635-640. doi: 10.21873/anticanres.14814.

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.

Keywords: Osteosarcoma; PDC; PDOX; green fluorescent protein; imaging; lung metastasis; metastasis; patient-derived cells; patient-derived orthotopic xenograft.

MeSH terms

  • Adolescent
  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Tracking
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / secondary*
  • Tibia / metabolism
  • Tibia / pathology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Green Fluorescent Proteins