Modelling the tumor metallome in vitro reveals manganese as a unique tumor-promoting element

Abstract

The microenvironment (TME) undergoes significant modification in tumor progression. TME comprises locally secreted molecules, cells, and metal ions. Metals interact with the cell surface or are internalized, modulating downstream pathways related to adhesion, migration, and proliferation. Our group showed that tumor-bearing mice present altered Mn distribution. Mn-exposed tumor cells showed in vitro higher proliferation and migration, associated with changes in glycocalyx organization. In this work, we modulated, in vitro, tumor cells metallome, and evaluated metals internalization, cellular distribution and its early effect on migration. Cell viability and survival were evaluated using the MTT and clonogenic assays. Metal retention and distribution were assessed with inductively coupled plasma optical emission spectroscopy (ICP-OES) and high-resolution X-ray fluorescence (XRF). Cell migration was evaluated with wound healing assay. Our results indicate that an early interaction between Mn and the cell surface, probably the negatively-charged glycocalyx, induces morphological changes that lead to increased invasiveness. Future investigations will help to better understand the mechanisms of Mn retention and internalization during tumor progression.