Patient-specific spheroids from squamous cell carcinoma of the head and neck region (HNSCC) as a tool for personalized therapy

Introduction 3D cell culture techniques have gained importance as preclinical models to analyze the response to targeted therapies in HNSCC. Our goal is to develop patient-specific spheroids that reflect the properties of the tumor tissue in order to be able to evaluate the response to drugs ("Personalized Medicine").

Methods Tissue samples from HNSCC patients (n=13) were processed into single cell suspensions by outgrowth culture or enzymatic digestion and seeded into spheroids. Light microscopic morphology evaluations and western blots (including Slug Snail) in passages 0-4 (P 0-4) were used to evaluate processes of the epithelial-mesenchymal transition (EMT). In order to test the influence of the passages on the therapy response, they were treated with cisplatin (0-50 μM) in P 1-3.

Results The success rate in transferring tumor cells into spheroids is effective with outgrowth culture (77.7%) and enzymatic digestion (66.6%). Compared to changes in morphology with passage, protein analysis does not indicate progression of EMT. The way in which the individual cells are obtained (outgrowth versus enzymatic digestion) influences the response to therapy. Cells isolated with outgrowth culture become more platinum-resistant with increasing passage, with enzymatic digestion -sensitive.

Discussion Cell culture models that accurately reflect the architecture of the original tumor are of immense importance on the way to "personalized medicine". Our results indicate that spheroids should be used for evaluation after P 1 at the latest. The method of single cell harvesting to produce spheroids influences the cellular characteristics.

Publication History

Article published online:
12 May 2023