In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 6 ( 2021-6-16), p. e0252577-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252577
DOI:
10.1371/journal.pone.0252577.g001
DOI:
10.1371/journal.pone.0252577.g002
DOI:
10.1371/journal.pone.0252577.g003
DOI:
10.1371/journal.pone.0252577.g004
DOI:
10.1371/journal.pone.0252577.g005
DOI:
10.1371/journal.pone.0252577.g006
DOI:
10.1371/journal.pone.0252577.s001
DOI:
10.1371/journal.pone.0252577.s002
DOI:
10.1371/journal.pone.0252577.s003
DOI:
10.1371/journal.pone.0252577.s004
DOI:
10.1371/journal.pone.0252577.s005
DOI:
10.1371/journal.pone.0252577.s006
DOI:
10.1371/journal.pone.0252577.r001
DOI:
10.1371/journal.pone.0252577.r002
DOI:
10.1371/journal.pone.0252577.r003
DOI:
10.1371/journal.pone.0252577.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3