Abstract 5151: Enhanced chemotactic response of MDA-MB-231 breast cancer cells towards stable gradients of EGF

Chemotactic cell migration is a basic mechanism underlying cancer cell invasion and hence metastasis. In this regard, growth factors such as epidermal growth factor (EGF) have been identified as guidance cues. Using ibidi's µ-Slide Chemotaxis we confirm the growth factor EGF as potent guidance cue for directional MDA-MB-231 migration in a physiological 3D environment. Moreover, we find enhanced sensitivity towards gradients of EGF in serum free media supplemented with defined protein composition (UltraCULTURETM). Combining defined, physiological migration conditions and enhanced sensitivity allowed us to quantify EGF dependent MDA-MB-231 chemotaxis in a detailed manor. MDA-MB-231 cells showed increased directional and kinetic response towards temporal and stable spatial gradients of EGF. While EGF guided directional migration was highly concentration dependent with a concentration optimum of 10 ng/mL, we found the chemokinetic effect induced by the presence of EGF being concentration independent. Those results suggest differential response of the migration and signal interpretation machinery of MDA-MB-231 cells. Both, blocking the ligand binding domain of the EGF-Receptor (EGFR) by a blocking antibody and inhibition of the kinase domain of EGFR by a small molecule inhibitor (AG1478) led to a reduction in EGF induced directional sensing and migration velocity. Additionally, low, non-effective single doses of antibody and small molecule inhibitor showed synergistically effective inhibition if combined. Those results support EGF being a potent guidance cue for MDA-MB-231 cell migration and help to understand the mechanisms behind chemotactic migration driven cancer metastasis. Citation Format: Nina Baumann, Verena Kuttenberger, Christine Huemmer, Jan Schwarz, Elias Horn Horn, Roman Zantl. Enhanced chemotactic response of MDA-MB-231 breast cancer cells towards stable gradients of EGF [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5151.