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Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system.
Simon, Karen A; Mosadegh, Bobak; Minn, Kyaw Thu; Lockett, Matthew R; Mohammady, Marym R; Boucher, Diane M; Hall, Amy B; Hillier, Shawn M; Udagawa, Taturo; Eustace, Brenda K; Whitesides, George M.
Afiliação
  • Simon KA; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
  • Mosadegh B; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 60 Oxford Street, Cambridge, MA 02138, USA; Dalio Institute of Cardiovascular Imaging, Department of Radiology, Weil
  • Minn KT; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
  • Lockett MR; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Department of Chemistry, University of North Carolina at Chapel Hill, 125 South Road, Chapel Hill, NC 27599, USA.
  • Mohammady MR; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
  • Boucher DM; Vertex Pharmaceuticals Incorporated, 50 Northern Blvd., Boston, MA 02210, USA.
  • Hall AB; Vertex Pharmaceuticals Incorporated, 50 Northern Blvd., Boston, MA 02210, USA.
  • Hillier SM; Vertex Pharmaceuticals Incorporated, 50 Northern Blvd., Boston, MA 02210, USA.
  • Udagawa T; Vertex Pharmaceuticals Incorporated, 50 Northern Blvd., Boston, MA 02210, USA.
  • Eustace BK; Vertex Pharmaceuticals Incorporated, 50 Northern Blvd., Boston, MA 02210, USA. Electronic address: brenda_eustace@vrtx.com.
  • Whitesides GM; Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 60 Oxford Street, Cambridge, MA 02138, USA. Electronic address: gwhitesides@gmwgroup.harvard.edu.
Biomaterials ; 95: 47-59, 2016 07.
Article em En | MEDLINE | ID: mdl-27116031
ABSTRACT
This work demonstrates the application of a 3D culture system-Cells-in-Gels-in-Paper (CiGiP)-in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct-prepared by stacking multiple sheets of paper containing cell-embedded hydrogels-generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Técnicas de Cultura de Células / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Técnicas de Cultura de Células / Neoplasias Pulmonares Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article