Back to Search
Start Over
Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response
- Source :
- Journal of Hematology & Oncology, Vol 13, Iss 1, Pp 1-15 (2020), Journal of Hematology & Oncology
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background The propensity of the activated neutrophils to form extracellular traps (NETs) is demonstrated in multiple inflammatory conditions. In this study, we investigated the roles of NETs in metastasis of hepatocellular carcinoma (HCC) and further explored the underlying mechanism of how NETs affect metastasis as well as the therapeutic value. Methods The neutrophils were isolated from the blood of human HCC patients and used to evaluate the formation of NETs. The expression of NET markers was detected in tumor specimens. A LPS-induced NET model was used to investigate the role of NETs on HCC metastasis. RNA-seq was performed to identify the key molecular event triggered by NETs, and their underlying mechanism and therapeutic significance were explored using both in vitro and in vivo assays. Results NET formation was enhanced in neutrophils derived from HCC patients, especially those with metastatic HCCs. NETs trapped HCC cells and subsequently induced cell-death resistance and enhanced invasiveness to trigger their metastatic potential, which was mediated by internalization of NETs into trapped HCC cells and activation of Toll-like receptors TLR4/9-COX2 signaling. Inhibition of TLR4/9-COX2 signaling abrogated the NET-aroused metastatic potential. A combination of DNase 1 directly wrecking NETs with anti-inflammation drugs aspirin/hydroxychloroquine effectively reduced HCC metastasis in mice model. Conclusions NETs trigger tumorous inflammatory response and fuel HCC metastasis. Targeting NETs rather than neutrophils themselves can be a practice strategy against HCC metastasis.
- Subjects :
- Male
Translation
Cancer Research
medicine.medical_specialty
Carcinoma, Hepatocellular
Extracellular Traps
lcsh:RC254-282
Metastasis
Hepatocellular carcinoma metastasis
In vivo
Internal medicine
medicine
Animals
Humans
Neoplasm Metastasis
Receptor
Molecular Biology
Inflammation
Hematology
lcsh:RC633-647.5
business.industry
Research
Liver Neoplasms
Inflammatory response
NETs
Hep G2 Cells
lcsh:Diseases of the blood and blood-forming organs
Neutrophil extracellular traps
HCCS
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
digestive system diseases
Mice, Inbred C57BL
Oncology
Hepatocellular carcinoma
Cancer research
TLR4
business
COX2
Subjects
Details
- ISSN :
- 17568722
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Journal of Hematology & Oncology
- Accession number :
- edsair.doi.dedup.....accaa31425c70ca0887599e3f2ebd7e2