Related Experiment Video
Updated: Apr 30, 2026
Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
Published on: January 7, 2019
Inhibition of macrophage polarization prohibits growth of human osteosarcoma
Qiang Xiao1, Xuepu Zhang, Yuexin Wu
1The Department of Hand and Foot Surgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Guta District, Jinzhou, 121001, China, qiang_xiao14@163.com.
Abstract:
Osteosarcoma is the most malignant bone tumor characterized by high local aggressiveness and poor therapeutic outcome. Tumor-associated macrophages (TAM) have been shown to participate in the development and progress of many types of cancer cells. However, whether TAM may play a role in the pathogenesis of osteosarcoma is largely unknown. In a mouse model of human osteosarcoma implantation, we showed that the recruited macrophages at the site of the implanted tumor were polarized to an M2 subtype (same as TAM) during the development and growth of the osteosarcoma. In a loss-of-function experiment, we deleted these TAM with a specific macrophage-eliminating liposome, which resulted in decreased tumor growth. Moreover, when the epidermal growth factor receptor (EGFR) in the implanted cancer cells was inhibited by shRNA, the tumor failed to grow in response to the recruited macrophages. Taken together, for the first time, we show that the growth of an osteosarcoma is EGFR signaling-dependent and TAM-mediated. Our data suggest that TAM and EGFR may be good targets for treating human osteosarcoma.
Insights
Tumor-associated macrophages (TAM) drive osteosarcoma growth by mediating epidermal growth factor receptor (EGFR) signaling. Eliminating TAM or inhibiting EGFR significantly reduced tumor progression in a mouse model, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Osteosarcoma is a highly aggressive bone cancer with limited treatment options.
- Tumor-associated macrophages (TAM) are implicated in various cancers, but their role in osteosarcoma is unclear.
Purpose of the Study:
- To investigate the role of TAM in osteosarcoma development.
- To explore the relationship between TAM and epidermal growth factor receptor (EGFR) signaling in osteosarcoma.
Main Methods:
- Utilized a mouse model of human osteosarcoma implantation.
- Administered a macrophage-eliminating liposome for TAM depletion (loss-of-function).
- Inhibited EGFR in cancer cells using shRNA.
Main Results:
- Recruited macrophages polarized to M2 subtype (TAM) during osteosarcoma growth.
- Macrophage depletion led to decreased tumor growth.
- EGFR inhibition abrogated tumor growth despite macrophage presence.
Conclusions:
- Osteosarcoma growth is dependent on both EGFR signaling and TAM mediation.
- TAM and EGFR represent potential therapeutic targets for osteosarcoma treatment.
