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Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.

Publication ,  Journal Article
Bushey, RT; Gottlin, EB; Campa, MJ; Patz, EF
Published in: PLoS One
2021

Exosomes are a class of extracellular vesicles (EVs) that are mediators of normal intercellular communication, but exosomes are also used by tumor cells to promote oncogenesis and metastasis. Complement factor H (CFH) protects host cells from attack and destruction by the alternative pathway of complement-dependent cytotoxicity (CDC). Here we show that CFH can protect exosomes from complement-mediated lysis and phagocytosis. CFH was found to be associated with EVs from a variety of tumor cell lines as well as EVs isolated from the plasma of patients with metastatic non-small cell lung cancer. Higher levels of CFH-containing EVs correlated with higher metastatic potential of cell lines. GT103, a previously described antibody to CFH that preferentially causes CDC of tumor cells, was used to probe the susceptibility of tumor cell-derived exosomes to destruction. Exosomes were purified from EVs using CD63 beads. Incubation of GT103 with tumor cell-derived exosomes triggered exosome lysis primarily by the classical complement pathway as well as antibody-dependent exosome phagocytosis by macrophages. These results imply that GT103-mediated exosome destruction can be triggered by antibody Fc-C1q interaction (in the case of lysis), and antibody-Fc receptor interactions (in the case of phagocytosis). Thus, this work demonstrates CFH is expressed on tumor cell derived exosomes, can protect them from complement lysis and phagocytosis, and that an anti-CFH antibody can be used to target tumor-derived exosomes for exosome destruction via innate immune mechanisms. These findings suggest that a therapeutic CFH antibody has the potential to inhibit tumor progression and reduce metastasis promoted by exosomes.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2021

Volume

16

Issue

6

Start / End Page

e0252577

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Complement
  • Phagocytosis
  • Neoplasm Staging
  • Membrane Glycoproteins
  • Macrophages
  • Lung Neoplasms
  • Leukocytes, Mononuclear
  • Immunity, Innate
  • Humans
 

Citation

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Bushey, R. T., Gottlin, E. B., Campa, M. J., & Patz, E. F. (2021). Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis. PLoS One, 16(6), e0252577. https://doi.org/10.1371/journal.pone.0252577
Bushey, Ryan T., Elizabeth B. Gottlin, Michael J. Campa, and Edward F. Patz. “Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.PLoS One 16, no. 6 (2021): e0252577. https://doi.org/10.1371/journal.pone.0252577.
Bushey RT, Gottlin EB, Campa MJ, Patz EF. Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis. PLoS One. 2021;16(6):e0252577.
Bushey, Ryan T., et al. “Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.PLoS One, vol. 16, no. 6, 2021, p. e0252577. Pubmed, doi:10.1371/journal.pone.0252577.
Bushey RT, Gottlin EB, Campa MJ, Patz EF. Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis. PLoS One. 2021;16(6):e0252577.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2021

Volume

16

Issue

6

Start / End Page

e0252577

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Complement
  • Phagocytosis
  • Neoplasm Staging
  • Membrane Glycoproteins
  • Macrophages
  • Lung Neoplasms
  • Leukocytes, Mononuclear
  • Immunity, Innate
  • Humans