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E-Cadherin loss associated with EMT promotes radioresistance in human tumor cells.
Theys, Jan; Jutten, Barry; Habets, Roger; Paesmans, Kim; Groot, Arjan J; Lambin, Philippe; Wouters, Brad G; Lammering, Guido; Vooijs, Marc.
Afiliación
  • Theys J; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Jutten B; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Habets R; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Paesmans K; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Groot AJ; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Lambin P; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Wouters BG; Department of Radiation Oncology (MAASTRO lab), Maastricht University Medical Centre, The Netherlands.
  • Lammering G; Ontario Cancer Institute and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Canada.
  • Vooijs M; Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Canada.
Radiother Oncol ; 99(3): 392-397, 2011 Jun.
Article en En | MEDLINE | ID: mdl-21680037
BACKGROUND AND PURPOSE: Hypoxia is a hallmark of solid cancers and associated with metastases and treatment failure. During tumor progression epithelial cells often acquire mesenchymal features, a phenomenon known as epithelial-to-mesenchymal transition (EMT). Intratumoral hypoxia has been linked to EMT induction. We hypothesized that signals from the tumor microenvironment such as growth factors and tumor oxygenation collaborate to promote EMT and thereby contribute to radioresistance. MATERIALS AND METHODS: Gene expression changes under hypoxia were analyzed using microarray and validated by qRT-PCR. Conversion of epithelial phenotype upon hypoxic exposure, TGFß addition or oncogene activation was investigated by Western blot and immunofluorescence. Cell survival following ionizing radiation was assayed using clonogenic survival. RESULTS: Upon hypoxia, TGFß addition or EGFRvIII expression, MCF7, A549 and NMuMG epithelial cells acquired a spindle shape and lost cell-cell contacts. Expression of epithelial markers such as E-cadherin decreased, whereas mesenchymal markers such as vimentin and N-cadherin increased. Combining hypoxia with TGFß or EGFRvIII expression, lead to more rapid and pronounced EMT-like phenotype. Interestingly, E-cadherin expression and the mesenchymal appearance were reversible upon reoxygenation. Mesenchymal conversion and E-cadherin loss were associated with radioresistance. CONCLUSIONS: Our findings describe a mechanism by which the tumor microenvironment may contribute to tumor radioresistance via E-cadherin loss and EMT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolerancia a Radiación / Cadherinas / Neoplasias Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Radiother Oncol Año: 2011 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolerancia a Radiación / Cadherinas / Neoplasias Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Radiother Oncol Año: 2011 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Irlanda