Introduction of a 3D-organotypic co-culture model for head and neck squamous cell carcinoma

Introduction:

Head and neck squamous cell carcinomas (HNSCC) are highly heterogeneous and vary in their response to therapy. A variety of targeted therapies is currently being established. There is an increasing need for innovative predictive models for the analysis of individual tumor responses. Epithelial-mesenchymal transition (EMT) is a cellular process that contributes to resistance development and is therefore relevant as a target for novel compounds. We introduce a new 3D organotypic co-culture (OTC) model to mimic the tumor in its entirety and to characterize invasive growth patterns as they arise during EMT.

Methods:

Vital tumor tissue was grown on dermal equivalents. A subgroup was additionally treated with fractionated irradiation. Expression of Ki-67, caspase-3, Pan-CK, p16, Programmed Death Ligand 1 (PD-L1), and Pan-CK/vimentin was evaluated by immunohistochemistry (IHC) and immunofluorescence (IF), respectively.

Results:

The 3D-OTC models were maintained in culture for up to 21 days and showed heterogeneous growth patterns at the invasive front, which were further determined by IF. The different invasion types correlated with the clinical behavior of the tumors. Markers for apoptosis and postradiogenic PD-L1 expression were determined.

Conclusions:

We describe for the first time a novel complex preclinical HNSCC model, which preserves the pathophysiology of paracrine tumor-stromal interactions and is suitable for the description of long-term effects of tumorigenesis, in particular invasion. The model allows the imitation of radiotherapy in order to assess the expression status of PD-L1, which is known to be postradiogenically upregulated.

Publication History

Publication Date:
23 April 2019 (online)