Smart surface selection of metastatic cancer cells
In collaboration with Prof. D. Bonifazi (Cardiff University) and Dr R. Marega
Peptides bearing the Ile-Gly-Asp (IGD) motif, a highly conserved sequence of fibronectin, are used for the preparation of anisotropic self-assembled monolayers (SAM gradients) to study the whole-population migratory behavior of metastatic breast cancer cells (MDA-MB-231 cells). IGDQ-exposing SAMs sustain the adhesion of MDA-MB-231 cells by triggering focal adhesion kinase phosphorylation. However, the biological responses of different cell lines interfaced with the SAM gradients show that only those exposing the IGDQ sequence induce significant migration of MDA-MB-231 cells. In particular, the observed migratory behavior suggests the presence of cell subpopulations associated with a “stationary” or a “migratory” phenotype, the latter determining a considerable cell migration at the sub-cm length scale.
The current project aims at understanding the mechanism underlying cancer cell migration on the extracellular matrix motif IGDQ exposed on these SAMs. The first part will be to interrogate the role of the different integrin subunits using siRNA-mediated silencing. Secondly, deep sequencing will allow the identification of genes whose expression is changed in these selected cells, which would explain their migratory phenotype. The role of these genes will then be investigated. These results will help to understand the metastatization process.
Selected publication
- Corvaglia V, Marega R, De Leo F, Michiels C & Bonifazi D 2016, ‘Unleashing Cancer Cells on Surfaces Exposing Motogenic IGDQ Peptides’ Small, vol 12, pp. 321-329.