Rhabdomyosarcoma (RMS) is the most common
soft tissue sarcoma in children. Success of current
therapies is still limited and outcome is particularly poor for metastatic
alveolar rhabdomyosarcoma (aRMS). We previously identified the
proprotein convertase furin as potential target for specific
drug delivery with RMS-homing
peptides.
Furin is a
protease that converts inactive precursor
proteins into bioactive
proteins and
peptides. In this study, we investigate the
biological role of
furin in aRMS progression in vitro and in vivo.
Furin expression was confirmed in over 86% RMS biopsies in a tissue microarray (n=89). Inducible
furin silencing in vitro led to significant impairment of cell viability and proliferation in all investigated aRMS cell lines, but not in MRC5 fibroblasts. Furthermore, the aRMS cell lines Rh3 and Rh4 revealed to be very sensitive to
furin silencing, undergoing
caspase-dependent cell death. Notably,
furin silencing in vivo led to complete remission of established Rh4
tumors and to delayed growth in Rh30
tumors. Taken together, these findings identify
furin as an important factor for aRMS progression and survival. Thus, we propose
furin as a novel therapeutic target for treatment of aRMS.