Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/12116 |
| _version_ | 1811181510029475840 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Deborah Morena |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:18:34Z |
| format | Article |
| id | doaj.art-c9dbb64a18db44239e47fcb7cf2149ed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:34Z |
| publishDate | 2016-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c9dbb64a18db44239e47fcb7cf2149ed2022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2016-03-01510.7554/eLife.12116Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypesDeborah Morena0Nicola Maestro1Francesca Bersani2Paolo Emanuele Forni3Marcello Francesco Lingua4Valentina Foglizzo5Petar Šćepanović6Silvia Miretti7Alessandro Morotti8Jack F Shern9Javed Khan10Ugo Ala11Paolo Provero12Valentina Sala13https://orcid.org/0000-0002-2283-2807Tiziana Crepaldi14Patrizia Gasparini15Michela Casanova16Andrea Ferrari17Gabriella Sozzi18Roberto Chiarle19Carola Ponzetto20Riccardo Taulli21https://orcid.org/0000-0003-1277-6263Department of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Veterinary Science, University of Turin, Grugliasco, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, ItalyPediatric Oncology Branch, Oncogenomics Section, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, United StatesPediatric Oncology Branch, Oncogenomics Section, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, United StatesDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, ItalyDepartment of Oncology, University of Turin, Turin, ItalyDepartment of Oncology, University of Turin, Turin, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyCeRMS, Center for Experimental Research and Medical Studies, Turin, Italy; Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, United StatesDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyDepartment of Oncology, University of Turin, Turin, Italy; CeRMS, Center for Experimental Research and Medical Studies, Turin, ItalyEmbryonal 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.https://elifesciences.org/articles/12116stem cell nicheHGF/met axisembryonal rhabdomyosarcomaundifferentiated pleomorphic sarcomaclonal evolutioncombination therapy |
| spellingShingle | 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 Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes eLife stem cell niche HGF/met axis embryonal rhabdomyosarcoma undifferentiated pleomorphic sarcoma clonal evolution combination therapy |
| title | Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| title_full | Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| title_fullStr | Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| title_full_unstemmed | Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| title_short | Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| title_sort | hepatocyte growth factor mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes |
| topic | stem cell niche HGF/met axis embryonal rhabdomyosarcoma undifferentiated pleomorphic sarcoma clonal evolution combination therapy |
| url | https://elifesciences.org/articles/12116 |
| work_keys_str_mv | AT deborahmorena hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT nicolamaestro hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT francescabersani hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT paoloemanueleforni hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT marcellofrancescolingua hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT valentinafoglizzo hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT petarscepanovic hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT silviamiretti hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT alessandromorotti hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT jackfshern hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT javedkhan hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT ugoala hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT paoloprovero hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT valentinasala hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT tizianacrepaldi hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT patriziagasparini hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT michelacasanova hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT andreaferrari hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT gabriellasozzi hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT robertochiarle hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT carolaponzetto hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes AT riccardotaulli hepatocytegrowthfactormediatedsatellitecellsnicheperturbationpromotesdevelopmentofdistinctsarcomasubtypes |