METAFIGHT · Understanding and fighting metastasis via dissection of the Core Invasive Machinery

The co-operative Metafight project will perform functional studies to understand the dissemination and outgrowth of metastasis through systematic analysis of the Core Invasive Machinery contained within integrin-mediated ECM attachment structure. It includes a large and discretely localised intracellular signalling network which drives migration and invasion. Our strategy is based on the hypothesis that metastatic cells arise from molecular changes that alter the primary tumour architecture as well as the tumor microenvironment, by reversible modulation of cell adhesion, onset of signalling pathways and acquisition of novel migratory and invasive capacities. The Metafight Consortium is strengthened by established combined expertise on adhesion receptor signalling and availability of unique tumor cell and cancer animal model systems. We will characterise known and novel components of the Core Invasive Machinery, responsible for development and homing of metastasis, by innovative in vivo non-invasive imaging techniques. The Metafight project comprises seven major interrelated Work Packages (WP). WP1 is designed to investigate the molecular and functional architecture of the Core Invasive Machinery, from which depends tumour cell migration and eventually invasion. WP2 and WP3 screen for key modulators of metastasis formation in in vivo murine models, by non-invasive imaging techniques. WP4 is related to a comprehensive proteomic analysis of expression and phosphorylation of our candidate modulators in metastasis formation. WP1-4 feed into WP5, which builds upon and exploits knowledge generated in the first four WPs and translates it into existing pharmacological interventions to generate new candidate drugs. This will lead to patent filing and licensing strategies. WP6 and WP7 handle dissemination and management activities. The ultimate accomplishment will include improvement of health, reduction of health expenses, as well as creation of new jobs and economic benefit.