Autologous Chemotaxis of Tumor Cells: a Novel Homing Mechanism to Lymphatics

Introduction Cell response to extracellular cues is often driven by gradients of morphogenetic and chemotactic proteins. Many of these proteins are secreted in extracellular matrix(ECM)-binding form to be subsequently released proteolytically, and here we explore how this feature, along with interstitial flow, which is present in all tissues, can affect pericellular morphogen gradients. We created an in silico model of mass transport for cells in a 3D porous ECM and examined the roles of flow, blocking antibodies, and paracrine signaling on calculated pericellular morphogen gradients. We also created an in vitro model of tumor cell metastasis using 3D tissue equivalents, tumor cells and lymphatic endothelial cells (LECs) to mimic conditions of the in silico model. The results of both models revealed the influence of interstitial flow, lending support to the hypothesis that interstitial flow can affect tumor migration through the spatial modification of biochemical cues.