gms | German Medical Science

Introduction: Therapeutic efficacy of EGFR inhibition with cetuximab is limitied due to selective susceptibility. This study aims to investigate the growth modifying effect of EGF und TGF-α in combination with cetuximab on HNSCC cell lines both in 2D and 3D tumor models.

Material and methods: PiCa and UPCI SCC154 cell lines were incubated with cetuximab alone and in combination with TGF-α and EGF, respectively. Proliferation of the cell cultures was observed up to 18 days in 2D (Eppendorf^® cell culture plate) and 3D models (Corning^® ultra-low attachment plate), respectively. Cell viability was evaluated using WST-8 assay, spheroids were additionally measured by planimetric assessment.

Results: Incubation of PiCa spheroids (n=27) with TGF-α and cetuximab, respectively, lead to decreased proliferation rates compared to control (p>0.001). In contrast, the viability of PiCa cell lines (n=30) in 2D cultures was influenced variably by TGF-α as their growth was first stimulated until day 4 (p=0.147) and later inhibited (p<0.001). Incubation with cetuximab showed a continuously decreased proliferation of the cells (p=0.032). Further, the growth inhibiting effect of cetuximab on spheroids (UPCI SCC154, n=10) was dependent on simultanous incubation of EGF as it was increased by suppressing EGF from day 11 onwards compared to constant EGF incubation (p>0.001).

Conclusion: The growth inhibiting effects of cetuximab seem to be influenced by interactions with simultanous autocrine EGFR ligands. Spheroids reveal deviant responses to cetuximab treatment compared to conventional 2D cultures and may therefore contribute to clarify the selective efficacy of cetuximab.