Tumour extracellular vesicle‐derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement‐dependent cytotoxicity of tumour cells
| Autor: | Sze Keong Tey, Yi Gao, Cherlie Lot Sum Yeung, Yi Man Eva Fung, Tung Him Ng, Xiaowen Mao, Angel Po Yee Ma, Edward F. Patz, Bonnie Hei Man Liu, Longyin Zhou, Peihua Cao, Judy Wai Ping Yam, Samuel Wan Ki Wong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Histology Carcinoma Hepatocellular Carcinogenesis Mice Nude Metastasis 03 medical and health sciences Extracellular Vesicles Mice 0302 clinical medicine Liver Neoplasms Experimental Cell Line Tumor medicine complement‐mediated cytotoxicity Animals Humans Neoplasm Metastasis Research Articles Mice Inbred BALB C biology Chemistry Cell Biology Extracellular vesicle hepatocellular carcinoma medicine.disease digestive system diseases Complement-dependent cytotoxicity eye diseases Complement system Neoplasm Proteins Immunosurveillance 030104 developmental biology 030220 oncology & carcinogenesis Factor H Complement Factor H Cancer research Alternative complement pathway biology.protein sense organs Antibody Research Article |
| Zdroj: | Journal of Extracellular Vesicles |
| ISSN: | 2001-3078 |
| Popis: | The complement system is involved in the immunosurveillance of pathogens and tumour cells. Proteomic profiling revealed that extracellular vesicles (EVs) released by metastatic hepatocellular carcinoma (HCC) cells contained a significant number of complement proteins. Complement Factor H (CFH), an abundant soluble serum protein that inhibits the alternative complement pathway, was found to be highly expressed in EVs of metastatic HCC cell lines. Here, we investigated the functional role of EV‐CFH and explored the therapeutic efficacy of targeting EV‐CFH with an anti‐CFH antibody in HCC. The results showed that EVs that are enriched in CFH promoted HCC cell growth, migration, invasiveness and enhanced liver tumour formation in mice. EV‐CFH also promoted metastasis, which was significantly abrogated when treated with an anti‐CFH antibody. These findings demonstrate an unexplored function of EV‐CFH in protecting HCC cells by evading complement attack, thereby facilitating tumorigenesis and metastasis. Lastly, we demonstrated the therapeutic efficacy of an anti‐CFH antibody in suppressing tumour formation in a syngeneic mouse model. This study suggests a new therapeutic strategy for HCC, by inhibiting EV‐CFH with a tumour specific anti‐CFH antibody. |
| Databáze: | OpenAIRE |
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