Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-β and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.

In the present work, porous gelatin scaffolds were prepared by insufflating an inert gas (argon) inside a concentrated solution of gelatin in the presence of a suitable polymeric surfactant in association with sodium dodecyl sulfate. The implementation of such an approach involved the design and manufacturing of a specially dedicated reactor. Foams were prepared at a temperature of 50 °C and then let gel at 4 °C. After purification, they were auto-cross-linked with EDC and freeze-dried. The scaffolds synthesised with this technique present a morphology characterised by pores of spherical symmetry highly interconnected by a plurality of interconnections and, as a consequence, are particularly suited for cell culturing. The dosage of the volume of the insufflated gas permits to modulate the scaffold pore and interconnect dimensions. In this way matrices characterised by void and interconnect average diameters ranging from 250 to 360 μm and from 80 to 150 μm, respectively, can be successfully obtained.