Hepatocyte growth factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes

Deborah Morena, Nicola Maestro, Francesca Bersani, Paolo Emanuele Forni, Marcello Francesco Lingua, Valentina Foglizzo, Petar Šćepanović, Silvia Miretti, Alessandro Morotti, Jack F. Shern, Javed Khan, Ugo Ala, Paolo Provero, Valentina Sala, Tiziana Crepaldi, Patrizia Gasparini, Michela Casanova, Andrea Ferrari, Gabriella Sozzi, Roberto ChiarleCarola Ponzetto, Riccardo Taulli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere12116
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
Publication statusPublished - Mar 17 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

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    Morena, D., Maestro, N., Bersani, F., Forni, P. E., Lingua, M. F., Foglizzo, V., Šćepanović, P., Miretti, S., Morotti, A., Shern, J. F., Khan, J., Ala, U., Provero, P., Sala, V., Crepaldi, T., Gasparini, P., Casanova, M., Ferrari, A., Sozzi, G., ... Taulli, R. (2016). Hepatocyte growth factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes. eLife, 5(MARCH2016), [e12116]. https://doi.org/10.7554/eLife.12116