RT Journal Article
SR Electronic
T1 Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 502
OP 516
DO 10.20892/j.issn.2095-3941.2020.0482
VO 18
IS 2
A1 Miserocchi, Giacomo
A1 Cocchi, Claudia
A1 De Vita, Alessandro
A1 Liverani, Chiara
A1 Spadazzi, Chiara
A1 Calpona, Sebastiano
A1 Di Menna, Giandomenico
A1 Bassi, Massimo
A1 Meccariello, Giuseppe
A1 De Luca, Giovanni
A1 Campobassi, Angelo
A1 Tumedei, Maria Maddalena
A1 Bongiovanni, Alberto
A1 Fausti, Valentina
A1 Cotelli, Franco
A1 Ibrahim, Toni
A1 Mercatali, Laura
YR 2021
UL http://www.cancerbiomed.org/content/18/2/502.abstract
AB Objective: Squamous cell carcinoma (SCC) represents the most common histotype of all head and neck malignancies and includes oropharyngeal squamous cell carcinoma (OSCC), a tumor associated with different clinical outcomes and linked to human papilloma virus (HPV) status. Translational research has few available in vitro models with which to study the different pathophysiological behavior of OSCCs. The present study proposes a 3-dimensional (3D) biomimetic collagen-based scaffold to mimic the tumor microenvironment and the crosstalk between the extracellular matrix (ECM) and cancer cells.Methods: We compared the phenotypic and genetic features of HPV-positive and HPV-negative OSCC cell lines cultured on common monolayer supports and on scaffolds. We also explored cancer cell adaptation to the 3D microenvironment and its impact on the efficacy of drugs tested on cell lines and primary cultures.Results: HPV-positive and HPV-negative cell lines were successfully grown in the 3D model and displayed different collagen fiber organization. The 3D cultures induced an increased expression of markers related to epithelial–mesenchymal transition (EMT) and to matrix interactions and showed different migration behavior, as confirmed by zebrafish embryo xenografts. The expression of hypoxia-inducible factor 1α (1α) and glycolysis markers were indicative of the development of a hypoxic microenvironment inside the scaffold area. Furthermore, the 3D cultures activated drug-resistance signaling pathways in both cell lines and primary cultures.Conclusions: Our results suggest that collagen-based scaffolds could be a suitable model for the reproduction of the pathophysiological features of OSCCs. Moreover, 3D architecture appears capable of inducing drug-resistance processes that can be studied to better our understanding of the different clinical outcomes of HPV-positive and HPV-negative patients with OSCCs.