Publikationsdatenbank

Ultrastructural changes of organoids from head and neck squamous cell carcinomas following irradiation (2022)

Art

Poster

Autoren

Fisch, Anne-Sophie (WE 1)

Tinhofer-Keilholz, Ingeborg

Plendl, Johanna (WE 1)

Kongress

Human 3D Organ Models : Networking-Event

Berlin, 24.08.2022

Quelle

Human 3D organ models : networking-event : abstracts — Charité, Universitätsmedizin Berlin (Hrsg.)

Berlin, 2022 — S. 9

Sprache

Englisch

Verweise

URL (Volltext): https://charite3r.charite.de/fileadmin/user_upload/microsites/ohne_AZ/sonstige/charite3r/Newsletter-Archiv/Abstract_collection_NetworkungEvent.pdf

Kontakt

Institut für Veterinär-Anatomie

Koserstr. 20
14195 Berlin
+49 30 838 75784
anatomie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Introduction:
Achieving personalization in radiation oncology requires adequate models. Important tools are organoids derived either from fresh tumor tissue specimens of cancer patients or derived subclones from cell lines with different radiosensitivity. Until now, there is only sparse information on the ultrastructure of these organoids. Therefore, we examined untreated and irradiated organoids by transmission electron microscopy to investigate ultrastructural effects of irradiation.

Methods:
Two patient-derived organoid models from head and neck squamous cell carcinoma (HNSCC) were irradiated with 0, 2 or 2 x 2 Gray. Seven days after delivering the final dose, the PDOs were processed for transmission electron microscopy. The same protocol was applied on the radiosensitive (C46) and
intermediate radioresistant (C78) subclones derived from the HNSCC cell line FaDu.

Results:
The PDOs recapitulate aspects of the ultrastructural morphology of poorly differentiated squamous cell carcinoma, such as high nuclear to cytoplasmic index, segmented nuclei, well developed cell organelles and nucleoli, high abundance of polyribosomes and low content of heterochromatin. The most striking ultrastructural changes in irradiated organoids included increased number of fragmented cells, heterolysosomes, lipid droplets and membrane blebs. Upon radiation the quantity of microvilli diminished in cells showing signs of apoptosis or necrosis. In FaDu C46, those features were already
detectable after a total dose of 2 Gy. The double dose was necessary to induce a comparable effect in FaDu C78.

Conclusion:
Transmission electron microscopy reveals distinct ultrastructural changes and different responses to radiotherapy, opening opportunities to study personal radioresistance mechanisms in more detail.