Objetivo Unlike mesenchymal migration, the amoeboid motility doesn’t require proteases and is an opportunistic movement of cancer cells which allows cells to glide through, rather than degrade, ECM barriers, using movements based on adaptations of the cell body. Preliminary experiments we conducted using a mixture of physiologic inhibitors of serine-proteases, metallo-proteases and cysteine-proteases, thus mimicking a physiological environment, showed no differences in vessel formation for both Endothelial Progenitor Cells (EPCs) and mature Endothelial Cells (ECs) under mesenchymal or amoeboid conditions. Thus, we hypothesized the existence of an “amoeboid angiogenesis”. We also hypothesized that the failure of cancer treatment using synthetic metalloproteinase inhibitors (MPIs) could be ascribed to the ability of cancer and ECs to skip the attack of the MPI therapy by allowing cancer invasion and blood vessel formation using the “amoeboid” strategy. Even the VEGFA targeting partially disregarded the expectations because of the resistance onset followed by the progression of the disease. Our preliminary experiments showed also an “indifference” of ECs and EPCs to VEGF stimulation under amoeboid conditions. Therefore, the aim of this project is to identify the multiple mechanisms shared by cancer cells and ECs/EPCs in the regulation of amoeboid movement, to identify common therapeutic strategies impairing vascular growth and cancer cell invasion at the same time, overcoming resistance to anti-VEGF and anti-protease therapy. The molecules identified (ephrin, protease receptors, etc.) will be used as candidates for targeted therapy through the delivery of cargo liposomes containing inhibitors of the connection of such molecules with the cortical actin cytoskeleton, in pre-clinical experiments with the perspective of a possible application to humans. We expect that this approach will give a progress in the treatment of tumors thus improving outcomes for cancer patients. Ámbito científico medical and health sciencesclinical medicineoncologyprostate cancermedical and health sciencesclinical medicineoncologybreast cancernatural sciencesbiological sciencesgeneticsmutation Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-GF - Global Fellowships Coordinador UNIVERSITA DEGLI STUDI DI FIRENZE Aportación neta de la UEn € 244 269,00 Dirección Piazza San Marco 4 50121 Florence Italia Ver en el mapa Región Centro (IT) Toscana Firenze Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 244 269,00 Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. THE REGENTS OF THE UNIVERSITY OF CALIFORNIA Estados Unidos Aportación neta de la UEn € 0,00 Dirección FRANKLIN STREET 1111 12 FLOOR 94607 OAKLAND CA Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 160 130,40
