PUBLICATION
Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis
- Authors
- Zhang, K., Liu, D., Zhao, J., Shi, S., He, X., Da, P., You, Y., You, B.
- ID
- ZDB-PUB-210530-1
- Date
- 2021
- Source
- Cell Death & Disease 12: 554 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Proliferation/physiology
- Disease Models, Animal
- Exosomes/metabolism*
- HMGB3 Protein/metabolism*
- Heterografts
- Human Umbilical Vein Endothelial Cells
- Humans
- Male
- Mice
- Mice, Nude
- Nasopharyngeal Carcinoma/blood supply*
- Nasopharyngeal Carcinoma/genetics
- Nasopharyngeal Carcinoma/metabolism
- Nasopharyngeal Carcinoma/pathology
- Nasopharyngeal Neoplasms/blood supply*
- Nasopharyngeal Neoplasms/genetics
- Nasopharyngeal Neoplasms/metabolism
- Nasopharyngeal Neoplasms/pathology
- Neoplasm Metastasis
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/pathology
- Up-Regulation
- Zebrafish
- PubMed
- 34050127 Full text @ Cell Death Dis.
Citation
Zhang, K., Liu, D., Zhao, J., Shi, S., He, X., Da, P., You, Y., You, B. (2021) Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis. Cell Death & Disease. 12:554.
Abstract
Distant metastasis accompanied by angiogenesis is the main cause of nasopharyngeal carcinoma (NPC)-related death. Nuclear exosomes (nEXOs) are potential tumour biomarkers. High mobility group box 3 (HMGB3), a nuclear protein, is known to be overexpressed in cancers. However, its role in NPC has not been elucidated. Here, we explore for the first time the function of nEXO HMGB3 in tumour angiogenesis involved in NPC metastasis using a series of in vitro experiments with NPC cell lines and clinical specimens and in vivo experiments with tumour xenograft zebrafish angiogenesis model. We found a high expression of HMGB3 in NPC, accompanied by the formation of micronuclei, to be associated with metastasis. Furthermore, the NPC-secreted HMGB3 expression was associated with tumour angiogenesis. Moreover, HMGB3-containing nEXOs, derived from the micronuclei of NPC cells, were ingested by the human umbilical vein endothelial cells (HUVECs), and accelerated angiogenesis in vitro and in vivo. Importantly, western blotting and flow cytometry analysis showed that circulating nEXO HMGB3 positively correlated with NPC metastasis. In summary, nEXO HMGB3 can be a significant biomarker of NPC metastasis and provide a novel basis for anti-angiogenesis therapy in clinical metastasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping