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Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia.
Vasquez, Ester Gil; Nasreddin, Nadia; Valbuena, Gabriel N; Mulholland, Eoghan J; Belnoue-Davis, Hayley L; Eggington, Holly R; Schenck, Ryan O; Wouters, Valérie M; Wirapati, Pratyaksha; Gilroy, Kathryn; Lannagan, Tamsin R M; Flanagan, Dustin J; Najumudeen, Arafath K; Omwenga, Sulochana; McCorry, Amy M B; Easton, Alistair; Koelzer, Viktor H; East, James E; Morton, Dion; Trusolino, Livio; Maughan, Timothy; Campbell, Andrew D; Loughrey, Maurice B; Dunne, Philip D; Tsantoulis, Petros; Huels, David J; Tejpar, Sabine; Sansom, Owen J; Leedham, Simon J.
Afiliación
  • Vasquez EG; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Nasreddin N; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Valbuena GN; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Mulholland EJ; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Belnoue-Davis HL; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Eggington HR; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Schenck RO; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Wouters VM; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Meibergdreef 9, 1105 Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 Amsterdam, the Netherlands.
  • Wirapati P; Swiss Institute for Bioinformatics, University of Lausanne, Lausanne, Switzerland.
  • Gilroy K; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Lannagan TRM; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Flanagan DJ; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Najumudeen AK; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Omwenga S; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK.
  • McCorry AMB; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
  • Easton A; Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Koelzer VH; Department of Pathology and Molecular Pathology, University and University Hospital Zürich, Rämistrasse 100, 8006 Zürich, Switzerland.
  • East JE; Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, and Oxford NIHR Biomedical Research Centre, Oxford, UK.
  • Morton D; Academic Department of Surgery, University of Birmingham, Birmingham, UK.
  • Trusolino L; Candiolo Cancer Institute FPO IRCCS, 10060 Candiolo, Torino, Italy.
  • Maughan T; Department of Oncology, Old Road Campus Research Building, Roosevelt Drive, University of Oxford, Oxford, UK.
  • Campbell AD; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Loughrey MB; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
  • Dunne PD; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
  • Tsantoulis P; University of Geneva and Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Huels DJ; Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, Meibergdreef 9, 1105 Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 Amsterdam, the Netherlands.
  • Tejpar S; Molecular Digestive Oncology Unit, KU Leuven, Leuven, Belgium.
  • Sansom OJ; Cancer Research UK Beatson Institute, Glasgow, UK; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow, UK.
  • Leedham SJ; Wellcome Centre Human Genetics, Roosevelt Drive, University of Oxford, Oxford, UK; Department of Pathology and Molecular Pathology, University and University Hospital Zürich, Rämistrasse 100, 8006 Zürich, Switzerland. Electronic address: simon.leedham@well.ox.ac.uk.
Cell Stem Cell ; 29(8): 1213-1228.e8, 2022 08 04.
Article en En | MEDLINE | ID: mdl-35931031
ABSTRACT
Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5-ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Mucosa Intestinal Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Mucosa Intestinal Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido