Clinical & Experimental Metastasis

, Volume 22, Issue 4, pp 319–329

An Orthotopic Model of Human Osteosarcoma Growth and Spontaneous Pulmonary Metastasis

  • Hue H. Luu
  • Quan Kang
  • Jong Kyung Park
  • Weike Si
  • Qing Luo
  • Wei Jiang
  • Hong Yin
  • Anthony G. Montag
  • Michael A. Simon
  • Terrance D. Peabody
  • Rex C. Haydon
  • Carrie W. Rinker-Schaeffer
  • Tong-Chuan He
Article

DOI: 10.1007/s10585-005-0365-9

Cite this article as:
Luu, H.H., Kang, Q., Park, J.K. et al. Clin Exp Metastasis (2005) 22: 319. doi:10.1007/s10585-005-0365-9

Abstract

Osteosarcoma is the most common primary malignancy of bone and patients often develop pulmonary metastases. In order to investigate the pathogenesis of human osteosarcoma, there is a great need to develop a clinically relevant animal model. Here we report the development of an osteosarcoma animal model using three related human osteosarcoma lines, the parental TE-85 and two derivative lines MNNG/HOS and 143B. In vitro characterization demonstrated that the 143B line had the greatest cell migration and the least cell adhesion activities among the three lines. The 143B line also exhibited the greatest ability for anchorage independent growth. When GFP-tagged osteosarcoma cells were injected into the proximal tibia of athymic mice, we found that 143B cells were highly tumorigenic and metastatic, and MNNG/HOS cells were tumorigenic but significantly less metastatic. TE85 cells were neither tumorigenic nor metastatic. The number of pulmonary metastases was found 50-fold higher in 143B injected animals than that in MNNG/HOS injected mice. No pulmonary metastases were detected in TE85 injected animals for up to 8 weeks. Primary tumors formed by MNNG/HOS and 143B cells could be visualized by whole body fluorescence imaging, while the pulmonary metastases were visualized on the necropsied samples. The GFP tagged 143B cells (and to a lesser extent, MNNG/HOS cells) were readily recovered from lung metastases. This clinically relevant model of human osteosarcoma provides varying degrees of tumor growth at the primary site and metastatic potential. Thus, this orthotopic model should be a valuable tool to investigate factors that promote or inhibit osteosarcoma growth and/or metastasis.

Key words

bone tumormetastasisprimary bone tumororthotopic animal modelosteosarcoma

Abbreviations

EMEM

minimum essential medium eagle

FCS

fetal calf serum

GFP

green fluorescent protein

hpf

high power field

PBS

phosphate buffered saline

Copyright information

© Springer 2005

Authors and Affiliations

  • Hue H. Luu
    • 1
  • Quan Kang
    • 1
    • 2
  • Jong Kyung Park
    • 1
    • 3
  • Weike Si
    • 1
    • 4
  • Qing Luo
    • 1
    • 2
  • Wei Jiang
    • 1
  • Hong Yin
    • 1
  • Anthony G. Montag
    • 1
    • 5
  • Michael A. Simon
    • 1
  • Terrance D. Peabody
    • 1
  • Rex C. Haydon
    • 1
  • Carrie W. Rinker-Schaeffer
    • 6
  • Tong-Chuan He
    • 1
  1. 1.Molecular Oncology Laboratory, Department of SurgeryThe University of Chicago Medical CenterChicagoUSA
  2. 2.The Children’s Hospital of Chongqing University of Medical SciencesChongqingChina
  3. 3.Department of Surgery, St. Paul’s Hospital, College of MedicineThe Catholic University of KoreaSeoulKorea
  4. 4.Department of Clinical BiochemistryThe Third Military Medical UniversityChongqingChina
  5. 5.Department of PathologyThe University of Chicago HospitalsChicagoUSA
  6. 6.Urological Research Laboratory, Department of SurgeryThe University of Chicago Medical CenterChicago