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

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 comp...

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Autores principales:	Ryan T Bushey, Elizabeth B Gottlin, Michael J Campa, Edward F Patz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d597752f28b949a08bce0754a7d74de1
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spelling	oai:doaj.org-article:d597752f28b949a08bce0754a7d74de12021-12-02T20:10:36ZComplement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.1932-620310.1371/journal.pone.0252577https://doaj.org/article/d597752f28b949a08bce0754a7d74de12021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252577https://doaj.org/toc/1932-6203Exosomes 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.Ryan T BusheyElizabeth B GottlinMichael J CampaEdward F PatzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252577 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryan T Bushey Elizabeth B Gottlin Michael J Campa Edward F Patz Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
description	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.
format	article
author	Ryan T Bushey Elizabeth B Gottlin Michael J Campa Edward F Patz
author_facet	Ryan T Bushey Elizabeth B Gottlin Michael J Campa Edward F Patz
author_sort	Ryan T Bushey
title	Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
title_short	Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
title_full	Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
title_fullStr	Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
title_full_unstemmed	Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
title_sort	complement factor h protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d597752f28b949a08bce0754a7d74de1
work_keys_str_mv	AT ryantbushey complementfactorhprotectstumorcellderivedexosomesfromcomplementdependentlysisandphagocytosis AT elizabethbgottlin complementfactorhprotectstumorcellderivedexosomesfromcomplementdependentlysisandphagocytosis AT michaeljcampa complementfactorhprotectstumorcellderivedexosomesfromcomplementdependentlysisandphagocytosis AT edwardfpatz complementfactorhprotectstumorcellderivedexosomesfromcomplementdependentlysisandphagocytosis
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Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.

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