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Updated: Jan 17, 2026
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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
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Neutrophil elastase promotes low molecular weight cyclin E1 formation to accelerate osteosarcoma proliferation
Jiuhui Xu1,2, Qianyu Shi1,2, Fanwei Zeng1,2
1Department of Musculoskeletal Tumor, Peking University People's Hospital, Beijing, China.
Frontiers in Immunology
|September 17, 2025
Summary
A low molecular weight cyclin E1 isoform (LMW-cyclin E1) drives osteosarcoma (OS) progression. Tumor-associated neutrophils release elastase (ELA2), which generates LMW-cyclin E1, promoting OS malignancy and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Osteosarcoma (OS) is a primary bone cancer with high metastatic potential.
- Cyclin E1 is known to be upregulated in OS.
- A novel cytoplasmic, low molecular weight cyclin E1 isoform (LMW-cyclin E1) is identified in OS.
Purpose of the Study:
- To investigate the role of LMW-cyclin E1 in osteosarcoma.
- To elucidate the mechanism of LMW-cyclin E1 formation.
- To explore the therapeutic potential of targeting neutrophil-osteosarcoma interactions.
Main Methods:
- RNA sequencing and Western blot to analyze cyclin E1 expression.
- Immunofluorescence and immunohistochemistry for validation.
- In vitro co-culture of neutrophils and OS cells, in vivo mouse models, and analysis of patient tissues.
Main Results:
- ELA2 from tumor-associated neutrophils cleaves full-length cyclin E1 into LMW-cyclin E1, accelerating OS proliferation.
- Neutrophil infiltration correlates with OS lung metastasis.
- OS cells induce neutrophil extracellular trap formation, amplifying ELA2 release.
Conclusions:
- LMW-cyclin E1 is a key driver of OS progression and metastasis.
- Neutrophil elastase (ELA2) is crucial for LMW-cyclin E1 generation.
- Targeting the crosstalk between neutrophils and osteosarcoma presents a promising therapeutic strategy.
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