Please use this identifier to cite or link to this item: doi:10.22028/D291-31952
Title: Organotypic Co-Cultures as a Novel 3D Model for Head and Neck Squamous Cell Carcinoma
Author(s): Engelmann, Luca
Thierauf, Julia
Koerich Laureano, Natalia
Stark, Hans-Juergen
Prigge, Elena-Sophie
Horn, Dominik
Freier, Kolja
Grabe, Niels
Rong, Chao
Federspil, Philippe
Zaoui, Karim
Plinkert, Peter K.
Rotter, Nicole
von Knebel Doeberitz, Magnus
Hess, Jochen
Affolter, Annette
Language: English
Title: Cancers
Volume: 12
Issue: 8
Publisher/Platform: MDPI
Year of Publication: 2020
Free key words: HNSCC
3D organotypic co-culture model
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Background: Head and neck squamous cell carcinomas (HNSCC) are phenotypically and molecularly heterogeneous and frequently develop therapy resistance. Reliable patient-derived 3D tumor models are urgently needed to further study the complex pathogenesis of these tumors and to overcome treatment failure. Methods: We developed a three-dimensional organotypic co-culture (3D-OTC) model for HNSCC that maintains the architecture and cell composition of the individual tumor. A dermal equivalent (DE), composed of healthy human-derived fibroblasts and viscose fibers, served as a scaffold for the patient sample. DEs were co-cultivated with 13 vital HNSCC explants (non-human papillomavirus (HPV) driven, n = 7; HPV-driven, n = 6). Fractionated irradiation was applied to 5 samples (non-HPV-driven, n = 2; HPV-driven n = 3). To evaluate expression of ki-67, cleaved caspase-3, pan-cytokeratin, p16INK4a, CD45, ∝smooth muscle actin and vimentin over time, immunohistochemistry and immunofluorescence staining were performed Patient checkup data were collected for up to 32 months after first diagnosis. Results: All non-HPV-driven 3D-OTCs encompassed proliferative cancer cells during cultivation for up to 21 days. Proliferation indices of primaries and 3D-OTCs were comparable and consistent over time. Overall, tumor explants displayed heterogeneous growth patterns (i.e., invasive, expansive, silent). Cancer-associated fibroblasts and leukocytes could be detected for up to 21 days. HPV DNA was detectable in both primary and 3D-OTCs (day 14) of HPV-driven tumors. However, p16INK4a expression levels were varying. Morphological alterations and radioresistant tumor cells were detected in 3D-OTC after fractionated irradiation in HPV-driven and non-driven samples. Conclusions: Our 3D-OTC model for HNSCC supports cancer cell survival and proliferation in their original microenvironment. The model enables investigation of invasive cancer growth and might, in the future, serve as a platform to perform sensitivity testing upon treatment to predict therapy response.
DOI of the first publication: 10.3390/cancers12082330
Link to this record: urn:nbn:de:bsz:291--ds-319522
ISSN: 2072-6694
Date of registration: 22-Jan-2021
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Zahn-, Mund- und Kieferheilkunde
Professorship: M - Prof. Dr. Kolja Freier
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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