TY - JOUR
T1 - Hepatocyte growth factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes
AU - Morena, Deborah
AU - Maestro, Nicola
AU - Bersani, Francesca
AU - Forni, Paolo Emanuele
AU - Lingua, Marcello Francesco
AU - Foglizzo, Valentina
AU - Šćepanović, Petar
AU - Miretti, Silvia
AU - Morotti, Alessandro
AU - Shern, Jack F.
AU - Khan, Javed
AU - Ala, Ugo
AU - Provero, Paolo
AU - Sala, Valentina
AU - Crepaldi, Tiziana
AU - Gasparini, Patrizia
AU - Casanova, Michela
AU - Ferrari, Andrea
AU - Sozzi, Gabriella
AU - Chiarle, Roberto
AU - Ponzetto, Carola
AU - Taulli, Riccardo
PY - 2016/3/17
Y1 - 2016/3/17
N2 - Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.
AB - Embryonal Rhabdomyosarcoma (ERMS) and Undifferentiated Pleomorphic Sarcoma (UPS) are distinct sarcoma subtypes. Here we investigate the relevance of the satellite cell (SC) niche in sarcoma development by using Hepatocyte Growth Factor (HGF) to perturb the niche microenvironment. In a Pax7 wild type background, HGF stimulation mainly causes ERMS that originate from satellite cells following a process of multistep progression. Conversely, in a Pax7 null genotype ERMS incidence drops, while UPS becomes the most frequent subtype. Murine EfRMS display genetic heterogeneity similar to their human counterpart. Altogether, our data demonstrate that selective perturbation of the SC niche results in distinct sarcoma subtypes in a Pax7 lineage-dependent manner, and define a critical role for the Met axis in sarcoma initiation. Finally, our results provide a rationale for the use of combination therapy, tailored on specific amplifications and activated signaling pathways, to minimize resistance emerging from sarcomas heterogeneity.
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UR - http://www.scopus.com/inward/citedby.url?scp=84961935854&partnerID=8YFLogxK
U2 - 10.7554/eLife.12116
DO - 10.7554/eLife.12116
M3 - Article
AN - SCOPUS:84961935854
VL - 5
JO - eLife
JF - eLife
SN - 2050-084X
IS - MARCH2016
M1 - e12116
ER -