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Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells.

Publication ,  Journal Article
Mao, X; Zhou, L; Tey, SK; Ma, APY; Yeung, CLS; Ng, TH; Wong, SWK; Liu, BHM; Fung, YME; Patz, EF; Cao, P; Gao, Y; Yam, JWP
Published in: J Extracell Vesicles
November 2020

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.

Duke Scholars

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Published In

J Extracell Vesicles

DOI

ISSN

2001-3078

Publication Date

November 2020

Volume

10

Issue

1

Start / End Page

e12031

Location

United States

Related Subject Headings

  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Liver Neoplasms, Experimental
  • Humans
  • Extracellular Vesicles
  • Complement Factor H
 

Citation

APA
Chicago
ICMJE
MLA
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Mao, X., Zhou, L., Tey, S. K., Ma, A. P. Y., Yeung, C. L. S., Ng, T. H., … Yam, J. W. P. (2020). Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells. J Extracell Vesicles, 10(1), e12031. https://doi.org/10.1002/jev2.12031
Mao, Xiaowen, Longyin Zhou, Sze Keong Tey, Angel Po Yee Ma, Cherlie Lot Sum Yeung, Tung Him Ng, Samuel Wan Ki Wong, et al. “Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells.J Extracell Vesicles 10, no. 1 (November 2020): e12031. https://doi.org/10.1002/jev2.12031.
Mao, Xiaowen, et al. “Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells.J Extracell Vesicles, vol. 10, no. 1, Nov. 2020, p. e12031. Pubmed, doi:10.1002/jev2.12031.
Mao X, Zhou L, Tey SK, Ma APY, Yeung CLS, Ng TH, Wong SWK, Liu BHM, Fung YME, Patz EF, Cao P, Gao Y, Yam JWP. Tumour extracellular vesicle-derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement-dependent cytotoxicity of tumour cells. J Extracell Vesicles. 2020 Nov;10(1):e12031.

Published In

J Extracell Vesicles

DOI

ISSN

2001-3078

Publication Date

November 2020

Volume

10

Issue

1

Start / End Page

e12031

Location

United States

Related Subject Headings

  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Liver Neoplasms, Experimental
  • Humans
  • Extracellular Vesicles
  • Complement Factor H