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Updated: Jan 20, 2026

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma
Published on: October 14, 2016
Targeting Clusterin Induces Apoptosis, Reduces Growth Ability and Invasion and Mediates Sensitivity to Chemotherapy
Xiaohui Wang1, Ying Yu2, Lingna Zang3
1Department of Orthopedics, Linyi Central Hospital, Linyi, Shandong 276000, China.
Objective:
The aim of the study was to investigate the expression of sCLU in relation to the clinicopathological features and prognosis of patients with untreated High-Grade Osteosarcoma (HGOS) and to evaluate sCLU as a target for osteosarcoma (OS) therapies.
Methods:
The expression of sCLU in 98 patients of HGOS enrolled from April 2005 to March 2015 at the affiliated hospital of Qingdao University was evaluated by immunohistochemistry. The sCLU expression, clinical data and survival were compared. siRNA-mediated sCLU gene silencing on cell apoptosis, viability, invasion and chemosensitivity to doxorubicin in U2OS cells in vitro was evaluated.
Results:
sCLU expression was found in 59 (60%) of the 98 patients. A positive correlation was observed between sCLU expression and metastatic disease (P = 0.036) and a negative correlation between sCLU expression and response to chemotherapy (P = 0.002). Targeting sCLU expression in U2OS cells induced significant reduction in cellular growth and higher rates of spontaneous endogenous apoptosis. In addition, targeting sCLU expression inhibited the invasion of U2OS cells. Furthermore, targeting sCLU expression significantly sensitized to chemotherapeutic drug, doxorubicin.
Conclusion:
The overexpression of sCLU was significantly correlated with metastasis and chemosensitivity in patients with HGOS. sCLU may be a promising therapeutic or chemopreventive target for human OS treatment.
Insights
High-Grade Osteosarcoma (HGOS) patients with higher soluble CLU (sCLU) expression showed increased metastasis and poorer chemotherapy response. Targeting sCLU may offer a new therapeutic strategy for osteosarcoma (OS).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- High-Grade Osteosarcoma (HGOS) is an aggressive bone cancer with limited treatment options.
- Soluble CLU (sCLU), a secreted form of Clusterin, has been implicated in various cancers, but its role in HGOS is not fully understood.
Purpose of the Study:
- To investigate the association between sCLU expression and clinicopathological features in HGOS patients.
- To evaluate sCLU as a potential therapeutic target for osteosarcoma (OS).
Main Methods:
- Immunohistochemistry was used to assess sCLU expression in 98 HGOS patient samples.
- Correlation analysis was performed between sCLU levels, clinical data, and patient survival.
- In vitro studies using U2OS cells evaluated the effects of sCLU gene silencing on apoptosis, viability, invasion, and chemosensitivity to doxorubicin.
Main Results:
- sCLU expression was detected in 60% of HGOS patients.
- Positive correlation between sCLU expression and metastatic disease (P = 0.036).
- Negative correlation between sCLU expression and response to chemotherapy (P = 0.002).
- In vitro, sCLU targeting reduced U2OS cell growth, increased apoptosis, inhibited invasion, and enhanced doxorubicin sensitivity.
Conclusions:
- Overexpressed sCLU is significantly correlated with metastasis and chemoresistance in HGOS.
- sCLU represents a promising therapeutic and chemopreventive target for osteosarcoma treatment.
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