To evaluate a non-invasive treatment to alter cancer cell motility by inducing focused shear waves at specific frequencies and amplitudes.The main cause of cancer mortality is metastasis, microenvironmental signals play a key role in this process, with such signals being (bio)chemical and mechanical in nature. Work has shown that mechanical forces (stresses), displacements (shear) and deformations can translate into biochemical signals affecting cancer cell survival. [1,2] Here we study a novel approach of utilizing oscillatory low frequency shear waves to non-invasively impact cancer cell metastasis, which we validate in vitro with the aim of going in vivo to observe changes in metastatic potential. MDA-MB231, metastatic human breast cancer cell line, was used for all experiments. Spheroids, used in the experimental set-up, mimic the behaviour and cell signalling of a solid tumour in the body. The formation of the spheroid was obtained using the spinning method in combination with the Corning® Ultra-Low Attachment Plates; every spheroid starts with 500 cells. After culturing the cells for 4 days spheroids were embedded into a bovine collagen type1 layer placed in a 2 well µ-plate at the position of highest shear stress (Fig.A, B). The 3-hour shaking treatment (frequency: 10Hz; displacement: 150µm) happened 14 hours after spheroid embedding. Spheroids were monitored over 3 days by taking pictures with a microscope. Magnetic resonance elastography was used to characterise the stiffness of bovine collagen type 1 to enable optimization (COMSOL 5.1 Multiphysics software) of the excitating frequency for generation of maximum shear stress pattern. Due to the simulation the spheroid was positioned in the area of the highest impact.Images C,D (taken at 56hs) show the impact on the metastatic spread of the spheroid after exposing it to a shear strain of 0.65 throughout 3 hours. Those spheroids which were exposed to the oscillatory shear strain showed 56 hours after the insult reduced cell spread behaviour (i.e. fewer cells) in comparison to the control spheroids. Detailed analysis showed that the shear stress also influences the ability of cell spread regarding the distance to the spheroid itself (E). Cells in the control are able to move further away from the spheroid than cells of the shaken one at the same timepoint. Additionally, treated spheroids start with a lower number of invasive cells in comparison to the control spheroid; this trend continues over the monitored time.The experiments showed that inducing shear stress over 3 hours impacts the behaviour of tumour cell spheroids in their ability of cancer cell spread. After the treatment the shaken spheroid starts with a reduced number of invading cells, in comparison to the control spheroid. After 24 and 32 hours the shaken spheroid appears to have a higher or same amount of cells, which left the spheroid, than the non-shaken one. This is due to the fact that the shaking not only causes inhibitory effects on the metastatic behaviour, but also a delay of progress in terms of the spheroid growth itself; the control spheroid reached a size where invasive cells are part of the spheroid and do not count as metastatic cells anymore. In conclusion we could show that altering the environment of the spheroid by inducing shear stress can cause an inhibitory effect on the cell spread of tumour spheroid. MR-Elastography allowed characterization of the gel properties and validation of the numerically calculated shear strain pattern.