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A Macrophage-Tumor Spheroid Co-Invasion Assay
Published on: January 24, 2025
Macrophage infiltration predicts a poor prognosis for human ewing sarcoma
Toshifumi Fujiwara1, Jun-ichi Fukushi, Shunsaku Yamamoto
1Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
The American Journal of Pathology
|July 21, 2011
Summary
Tumor-associated macrophages (TAMs) promote Ewing sarcoma progression by stimulating blood vessel growth and bone breakdown. Depleting TAMs inhibited tumor development, suggesting they are a therapeutic target for this aggressive cancer.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Ewing sarcoma-primitive neuroectodermal tumor (EWS) is a rare and aggressive primary musculoskeletal tumor with a poor prognosis.
- The role of tumor-associated macrophages (TAMs) in the development and progression of EWS remains largely unexplored.
Purpose of the Study:
- To investigate the impact of TAMs on EWS development and progression.
- To explore the potential of targeting TAMs for EWS therapy.
Main Methods:
- TAMs were isolated from mouse xenografts and analyzed for cytokine expression and osteoclastic differentiation.
- TAMs were depleted using liposome-encapsulated clodronate in mouse models.
- Macrophage infiltration and tumor vascularity were assessed in human EWS samples.
- Survival analysis was performed using Kaplan-Meier methods.
Main Results:
- TAMs in mouse EWS xenografts expressed elevated levels of pro-inflammatory cytokines (IL-6, KC, MCP-1).
- TAMs exhibited enhanced osteoclastic differentiation capacity compared to normal monocytes.
- Depletion of TAMs significantly suppressed EWS xenograft growth.
- In human EWS, higher macrophage infiltration (CD68+) correlated with poorer overall survival, increased vascularity, elevated C-reactive protein, and higher white blood cell counts.
Conclusions:
- TAMs contribute to EWS progression by promoting angiogenesis and osteoclastogenesis.
- Targeting TAMs represents a promising therapeutic strategy for Ewing sarcoma.
