Investigation of cell mechanics and migration on DDR2-expressing neuroblastoma cell line

Neuroblastoma is a devastating disease accounting for ~15% of all childhood cancer deaths. Collagen content and fiber association within the tumor stroma influence tumor progression and metastasis. High expression levels of collagen receptor kinase, Discoidin domain receptor II (DDR2), are associated with poor survival of neuroblastoma patients. Additionally, cancer cells generate and sustain mechanical forces within their enviroment as a part of their normal physiology. Despite this, whether collagen activated DDR2 signaling dysregulate these migration forces is still elusive. To address these questions, a shRNA DDR2 knockdown neuroblastoma cell line (SH-SY5Y) was engineered to evaluate the consequence of DDR2 on cellular mechanics. Atomic force microscopy and traction force microscopy were utlizing to unveil the biophysical altercations. DDR2 down-regulation was found to significantly reduce proliferation, cell stiffness, and cellular elongation. Aditionally, DDR2 down-regulated cells had decreased traction forces when plated on collagen coated elastic substrates. Together, these results highlight the important role that DDR2 has in reducing migration mechanics in neuroblastoma and might be a promising target for future therapies.