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Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages

Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages
Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages

Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome. Furthermore, the size of the phagosome-associated vacuole is increased by inhibition of the mTOR pathway. Collectively, the identification of this vacuolar compartment has implications for understanding the subcellular trafficking processes leading to the destruction of phagocytosed, antibody-opsonized cancer cells by macrophages.

antibodies, lysosome, macrophages, phagosome, vacuole
1398-9219
273-284
Velmurugan, Ramraj
4f2d41cd-90eb-4f61-b5e0-df6308726d28
Ramakrishnan, Sreevidhya
a36e091c-e3ca-42cc-aa83-f2fe3aa2f950
Kim, Mingin
c8f137a8-14e1-4e26-be52-d9d9287a77d9
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Velmurugan, Ramraj
4f2d41cd-90eb-4f61-b5e0-df6308726d28
Ramakrishnan, Sreevidhya
a36e091c-e3ca-42cc-aa83-f2fe3aa2f950
Kim, Mingin
c8f137a8-14e1-4e26-be52-d9d9287a77d9
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Velmurugan, Ramraj, Ramakrishnan, Sreevidhya, Kim, Mingin, Ober, Raimund J. and Ward, E. Sally (2018) Phagocytosis of antibody-opsonized tumor cells leads to the formation of a discrete vacuolar compartment in macrophages. Traffic, 19 (4), 273-284. (doi:10.1111/tra.12552).

Record type: Article

Abstract

Despite the rapidly expanding use of antibody-based therapeutics to treat cancer, knowledge of the cellular processes following phagocytosis of antibody-opsonized tumor cells is limited. Here we report the formation of a phagosome-associated vacuole that is observed in macrophages as these degradative compartments mature following phagocytosis of HER2-positive cancer cells in the presence of the HER2-specific antibody, trastuzumab. We demonstrate that this vacuole is a distinct organelle that is closely apposed to the phagosome. Furthermore, the size of the phagosome-associated vacuole is increased by inhibition of the mTOR pathway. Collectively, the identification of this vacuolar compartment has implications for understanding the subcellular trafficking processes leading to the destruction of phagocytosed, antibody-opsonized cancer cells by macrophages.

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Accepted/In Press date: 26 January 2018
e-pub ahead of print date: 13 February 2018
Published date: 1 April 2018
Keywords: antibodies, lysosome, macrophages, phagosome, vacuole

Identifiers

Local EPrints ID: 423684
URI: http://eprints.soton.ac.uk/id/eprint/423684
ISSN: 1398-9219
PURE UUID: 8a2b21a7-6271-4386-a485-ab3381f985ee
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 27 Sep 2018 16:30
Last modified: 18 Mar 2024 03:48

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Contributors

Author: Ramraj Velmurugan
Author: Sreevidhya Ramakrishnan
Author: Mingin Kim
Author: Raimund J. Ober ORCID iD
Author: E. Sally Ward ORCID iD

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