Related Experiment Video
Updated: Apr 26, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
GLI2 is a novel therapeutic target for metastasis of osteosarcoma
Hiroko Nagao-Kitamoto1, Masahito Nagata, Satoshi Nagano
1Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Abstract:
Aberrant activation of the Hedgehog (Hh) pathway has been reported in several malignancies. We previously demonstrated that knockdown of GLI2 inhibited proliferation of osteosarcoma cells through regulation of the cell cycle. In this study, we analyzed the function of GLI2 in the pathogenesis of osteosarcoma metastasis. Immunohistochemical studies showed that GLI2 was overexpressed in patient osteosarcoma specimens. Knockdown of GLI2 inhibited migration and invasion of osteosarcoma cells. In contrast, the forced expression of constitutively active GLI2 in mesenchymal stem cells promoted invasion. In addition, xenograft models showed that knockdown of GLI2 decreased lung metastasis of osteosarcomas. To examine clinical applications, we evaluated the efficacy of arsenic trioxide (ATO), which is a Food and Drug Administration-approved antitumor drug, on osteosarcoma cells. ATO treatment suppressed the invasiveness of osteosarcoma cells by inhibiting the transcriptional activity of GLI2. In addition, the combination of Hh inhibitors including ATO, vismodegib and GANT61 prevented migration and metastasis of osteosarcoma cells. Consequently, our findings suggested that GLI2 regulated metastasis as well as the progression of osteosarcomas. Inhibition of the GLI2 transcription may be an effective therapeutic method for preventing osteosarcoma metastasis.
Insights
Aberrant activation of the Hedgehog (Hh) pathway and GLI2 overexpression drive osteosarcoma metastasis. Inhibiting GLI2 transcription with drugs like arsenic trioxide shows promise for preventing cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant activation of the Hedgehog (Hh) pathway is implicated in various cancers.
- GLI2, a key transcription factor in the Hh pathway, was previously shown to regulate osteosarcoma cell proliferation.
- The role of GLI2 in osteosarcoma metastasis remained to be elucidated.
Purpose of the Study:
- To investigate the function of GLI2 in osteosarcoma metastasis.
- To evaluate the therapeutic potential of targeting GLI2 for osteosarcoma treatment.
Main Methods:
- Immunohistochemical analysis of GLI2 expression in patient osteosarcoma specimens.
- In vitro studies involving GLI2 knockdown and forced expression in osteosarcoma and mesenchymal stem cells.
- In vivo xenograft models to assess the effect of GLI2 knockdown on lung metastasis.
- Evaluation of arsenic trioxide (ATO) and other Hh inhibitors on osteosarcoma cell invasiveness and GLI2 transcriptional activity.
Main Results:
- GLI2 was significantly overexpressed in osteosarcoma tissues.
- GLI2 knockdown inhibited osteosarcoma cell migration and invasion, while its forced expression promoted invasion.
- Knockdown of GLI2 reduced lung metastasis in xenograft models.
- ATO suppressed osteosarcoma cell invasiveness by inhibiting GLI2 transcriptional activity.
- Combined Hh inhibitors (ATO, vismodegib, GANT61) effectively prevented osteosarcoma cell migration and metastasis.
Conclusions:
- GLI2 plays a critical role in regulating both the progression and metastasis of osteosarcomas.
- Inhibition of GLI2 transcription represents a potential therapeutic strategy to prevent osteosarcoma metastasis.
- Targeting the Hh pathway, particularly GLI2, offers a promising avenue for osteosarcoma treatment.
More Related Videos
04:25Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
08:47Improved Visualization of Lung Metastases at Single Cell Resolution in Mice by Combined In-situ Perfusion of Lung Tissue and X-Gal Staining of lacZ-Tagged Tumor Cells
Published on: August 21, 2012
