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doi:10.22028/D291-31952
Titel: | Organotypic Co-Cultures as a Novel 3D Model for Head and Neck Squamous Cell Carcinoma |
VerfasserIn: | 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 |
Sprache: | Englisch |
Titel: | Cancers |
Bandnummer: | 12 |
Heft: | 8 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2020 |
Freie Schlagwörter: | HNSCC 3D organotypic co-culture model invasion HPV |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
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 der Erstveröffentlichung: | 10.3390/cancers12082330 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-319522 hdl:20.500.11880/30417 http://dx.doi.org/10.22028/D291-31952 |
ISSN: | 2072-6694 |
Datum des Eintrags: | 22-Jan-2021 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Materials |
In Beziehung stehendes Objekt: | http://www.mdpi.com/2072-6694/12/8/2330/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Zahn-, Mund- und Kieferheilkunde |
Professur: | M - Prof. Dr. Kolja Freier |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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cancers-12-02330.pdf | 7,29 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons