Chemotherapy-induced release of ADAM17 bearing EV as a potential resistance mechanism in ovarian cancer

Hugendieck G, Lettau M, Andreas S, Neumann S, Reinhardt N, Arnold P, Theilig F, Bastian L, Rogmans C, Weimer JP, Flörkemeier I, Wesch D, Arnold N, Maass N, Janssen O, Bauerschlag D, Hedemann N (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Journal of Extracellular Vesicles Co-Action Publishing

Book Volume: 12

Article Number: 12338

Journal Issue: 7

DOI: 10.1002/jev2.12338

Abstract

Ovarian cancer (OvCa) is the gynaecological disorder with the poorest prognosis due to the fast development of chemoresistance. We sought to connect chemoresistance and cancer cell-derived extracellular vesicles (EV). The mechanisms of how chemoresistance is sustained by EV remained elusive. One potentially contributing factor is A Disintegrin and Metalloprotease 17 (ADAM17)—itself being able to promote chemoresistance and inducing tumour cell proliferation and survival via the Epidermal Growth Factor Receptor (EGFR) pathway by shedding several of its ligands including Amphiregulin (AREG). We now demonstrate that upon chemotherapeutic treatment, proteolytically active ADAM17 is released in association with EV from OvCa cells. In terms of function, we show that patient-derived EV induce AREG shedding and restore chemoresistance in ADAM17-deficient cells. Confirming that ADAM17-containing EV transmit chemoresistance in OvCa, we propose that ADAM17 levels (also on EV) might serve as an indicator for tumour progression and the chemosensitivity status of a given patient.

Authors with CRIS profile

Philipp Arnold Lehrstuhl für Funktionelle und Klinische Anatomie

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

Hugendieck, G., Lettau, M., Andreas, S., Neumann, S., Reinhardt, N., Arnold, P.,... Hedemann, N. (2023). Chemotherapy-induced release of ADAM17 bearing EV as a potential resistance mechanism in ovarian cancer. Journal of Extracellular Vesicles, 12(7). https://doi.org/10.1002/jev2.12338

MLA:

Hugendieck, Gerrit, et al. "Chemotherapy-induced release of ADAM17 bearing EV as a potential resistance mechanism in ovarian cancer." Journal of Extracellular Vesicles 12.7 (2023).

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