Neutrophil elastase promotes low molecular weight cyclin E1 formation to accelerate osteosarcoma proliferation
Mechanistically, we found that ELA2, primarily derived from tumor-associated neutrophils, cleaves full-length cyclin E1 to generate LMW-cyclin E1, which accelerates OS proliferation. Moreover, neutrophil infiltration was associated with OS lung metastasis. OS cells also induced neutrophil extracellular trap formation, which further amplified ELA2 release. Depleting neutrophils or inhibiting ELA2 significantly suppressed OS malignancy. Hence, targeting neutrophil-osteosarcoma crosstalk may be a potential novel therapeutic strategy.
Authors
- Xiaodong Tang (ORCID: https://orcid.org/0000-0003-0463-5487)
- Fanwei Zeng (ORCID: https://orcid.org/0009-0002-5083-7573)
- Jiuhui Xu (ORCID: https://orcid.org/0000-0002-1248-3746)
- Qianyu Shi (ORCID: https://orcid.org/0000-0001-7860-0143)
- Tingting Ren (ORCID: https://orcid.org/0000-0002-6226-6504)
- Ran Wei (ORCID: https://orcid.org/0000-0001-6095-7419)
Institutions
- Peking University (CN)
- Peking University People's Hospital (CN)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-09-01
- DOI
- https://doi.org/10.3389/fimmu.2025.1647913
- Citations
- 1
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Natural Science Foundation of China
- Peking University
- Peking University People's Hospital