"The MICROENVIMET project proposes innovative approaches for building a comprehensive understanding of the interplay between cancer cells and their microenvironment both at primary and secondary sites. The objectives are to identify molecular pathways involved in the regulation of metastatic dissemination to lung, liver, lymph node and bone. To achieve these objectives, the original experimental approach proposed is to modulate the production/activity of proteases or their inhibitors. Proteases are now recognized as key regulators of a complex network of interacting molecules that modulate the properties of cancer cells and their microenvironment. The project is intended to identify key molecular pathways underlying early steps of metastatic dissemination by interfering with the protease network and studying the impact of such experimentally manipulated microenvironment on metastasis formation. In addition to identifying key regulators of metastasis, we aim at developing blocking antibodies towards these new candidates, with efficacy for therapeutic intervention, by using the most advanced state-of-the-art technologies. The study of cancer stem cells will be integrated into current concepts that consider and attempt to explain the importance of the microenvironment during cancer progression. The 9 academic and 1 SME Participants will combine expertise in genomics, proteomics, bioinformatics, in vivo imaging, transgenic mice, mouse models of metastasis, genetic manipulation of transplantable tumour cells, computerized image analysis, virus-mediated gene transfer, phage display and production of neutralizing antibodies. This consortium will facilitate shared access to a new microRNA platform, innovative technologies, human tumour tissue banks, in vivo and in vitro models mimicking different steps of metastatic dissemination, as well as know how in tumour-host cell interplay, angiogenesis, lymphangiogenesis, cancer stem cell biology and generation of database."