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Cellular origin and clonal evolution of human dedifferentiated liposarcoma.
Gruel, Nadège; Quignot, Chloé; Lesage, Laëtitia; El Zein, Sophie; Bonvalot, Sylvie; Tzanis, Dimitri; Ait Rais, Khadija; Quinquis, Fabien; Manciot, Bastien; Vibert, Julien; El Tannir, Nadine; Dahmani, Ahmed; Derrien, Héloïse; Decaudin, Didier; Bièche, Ivan; Courtois, Laura; Mariani, Odette; Linares, Laëtitia K; Gayte, Laurie; Baulande, Sylvain; Waterfall, Joshua J; Delattre, Olivier; Pierron, Gaëlle; Watson, Sarah.
Afiliação
  • Gruel N; INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
  • Quignot C; Department of Translational Research, Institut Curie Research Center, Paris, France.
  • Lesage L; INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
  • El Zein S; Department of Pathology, Institut Curie Hospital, Paris, France.
  • Bonvalot S; Department of Pathology, Institut Curie Hospital, Paris, France.
  • Tzanis D; Department of Surgical Oncology, Institut Curie Hospital, Paris, France.
  • Ait Rais K; Department of Surgical Oncology, Institut Curie Hospital, Paris, France.
  • Quinquis F; Department of Genetics, Institut Curie Hospital, Paris, France.
  • Manciot B; Department of Genetics, Institut Curie Hospital, Paris, France.
  • Vibert J; INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
  • El Tannir N; INSERM U830, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Center, Paris, France.
  • Dahmani A; Drug Development Department, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.
  • Derrien H; Medico Scientific Program for Adult sarcomas, Institut Curie Research Center, Paris, France.
  • Decaudin D; Laboratory of Preclinical Investigation, Department of translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Bièche I; Laboratory of Preclinical Investigation, Department of translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Courtois L; Laboratory of Preclinical Investigation, Department of translational Research, PSL Research University, Institut Curie Research Center, Paris, France.
  • Mariani O; Department of Medical Oncology, Institut Curie Hospital, Paris, France.
  • Linares LK; Department of Genetics, Institut Curie Hospital, Paris, France.
  • Gayte L; Department of Genetics, Institut Curie Hospital, Paris, France.
  • Baulande S; Department of Pathology, Institut Curie Hospital, Paris, France.
  • Waterfall JJ; INSERM U1194, Metabolism and Sarcoma, Institut de Recherche en Cancérologie de Montpellier, Université de Montpellier, Montpellier, France.
  • Delattre O; INSERM U1194, Metabolism and Sarcoma, Institut de Recherche en Cancérologie de Montpellier, Université de Montpellier, Montpellier, France.
  • Pierron G; Institut Curie Genomics of Excellence (ICGex) Platform, PSL Research University, Institut Curie, Paris, France.
  • Watson S; Department of Translational Research, Institut Curie Research Center, Paris, France.
Nat Commun ; 15(1): 7941, 2024 Sep 12.
Article em En | MEDLINE | ID: mdl-39266532
ABSTRACT
Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-ß-high immunosuppressive tumor micro-environment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Proteínas Proto-Oncogênicas c-mdm2 / Microambiente Tumoral / Evolução Clonal / Lipossarcoma Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adipócitos / Proteínas Proto-Oncogênicas c-mdm2 / Microambiente Tumoral / Evolução Clonal / Lipossarcoma Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França País de publicação: Reino Unido