Organotypic co-cultures as a novel 3D model for head and neck squamous cell carcinoma

• Verfasst von: Engelmann, Luca [VerfasserIn]
• Verfasst von: Thierauf, Julia [VerfasserIn]
• Verfasst von: Laureano, Natalia K. [VerfasserIn]
• Verfasst von: Stark, Hans-Jürgen [VerfasserIn]
• Verfasst von: Prigge, Elena-Sophie [VerfasserIn]
• Verfasst von: Horn, Dominik [VerfasserIn]
• Verfasst von: Freier, Kolja [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Rong, Chao [VerfasserIn]
• Verfasst von: Federspil, Philippe A. [VerfasserIn]
• Verfasst von: Plath, Karim [VerfasserIn]
• Verfasst von: Plinkert, Peter K. [VerfasserIn]
• Verfasst von: Rotter, Nicole [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Verfasst von: Heß, Jochen [VerfasserIn]
• Verfasst von: Affolter, Annette [VerfasserIn]
• Titel: Organotypic co-cultures as a novel 3D model for head and neck squamous cell carcinoma
• Verf.angabe: Luca Engelmann, Julia Thierauf, Natalia Koerich Laureano, Hans-Juergen Stark, Elena-Sophie Prigge, Dominik Horn, Kolja Freier, Niels Grabe, Chao Rong, Philippe Federspil, Karim Zaoui, Peter K. Plinkert, Nicole Rotter, Magnus von Knebel Doeberitz, Jochen Hess and Annette Affolter
• E-Jahr: 2020
• Jahr: 18 August 2020
• Umfang: 20 S.
• Fussnoten: Gesehen am 14.12.2020
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2020
• Band/Heft Quelle: 12(2020,8) Artikel-Nummer 2330, 20 Seiten
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers12082330
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 3D organotypic co-culture model
• Sach-SW: HNSCC
• Sach-SW: HPV
• Sach-SW: invasion
• K10plus-PPN: 1742725082

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.