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 Chiarle; Carola Ponzetto; Riccardo Taulli

doi:10.7554/eLife.12116

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

Fondazione IRCCS Istituto Nazionale dei Tumori

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	e12116
Journal	eLife
Volume	5
Issue number	MARCH2016
DOIs	https://doi.org/10.7554/eLife.12116
Publication status	Published - Mar 17 2016

ASJC Scopus subject areas

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

Access to Document

10.7554/eLife.12116

Cite this

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

Morena, D, Maestro, N, Bersani, F, Forni, PE, Lingua, MF, Foglizzo, V, Šćepanović, P, Miretti, S, Morotti, A, Shern, JF, Khan, J, Ala, U, Provero, P, Sala, V, Crepaldi, T, Gasparini, P , Casanova, M , Ferrari, A , Sozzi, G, Chiarle, R, Ponzetto, C & Taulli, R 2016, 'Hepatocyte growth factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes', eLife, vol. 5, no. MARCH2016, e12116. https://doi.org/10.7554/eLife.12116

@article{3063317ee6714ba1a5851fd8237ff517,

title = "Hepatocyte growth factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes",

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.",

author = "Deborah Morena and Nicola Maestro and Francesca Bersani and Forni, {Paolo Emanuele} and Lingua, {Marcello Francesco} and Valentina Foglizzo and Petar {\v S}{\'c}epanovi{\'c} and Silvia Miretti and Alessandro Morotti and Shern, {Jack F.} and Javed Khan and Ugo Ala and Paolo Provero and Valentina Sala and Tiziana Crepaldi and Patrizia Gasparini and Michela Casanova and Andrea Ferrari and Gabriella Sozzi and Roberto Chiarle and Carola Ponzetto and Riccardo Taulli",

year = "2016",

month = mar,

day = "17",

doi = "10.7554/eLife.12116",

language = "English",

volume = "5",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

number = "MARCH2016",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84961935854&partnerID=8YFLogxK

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 -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this