Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro
Summary: Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase...
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doaj-31caf4f495074ab288431229b2f9c5472020-11-25T01:31:30ZengElsevierCell Reports2211-12472017-10-01212508516Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In VitroBryan A. Hassell0Girija Goyal1Esak Lee2Alexandra Sontheimer-Phelps3Oren Levy4Christopher S. Chen5Donald E. Ingber6Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USAWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USAWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA; Department of Biomedical Engineering and the Biological Design Center, Boston University, Boston, MA 02215, USAWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA; Department of Biology, University of Freiburg, Freiburg, GermanyWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USAWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA; Department of Biomedical Engineering and the Biological Design Center, Boston University, Boston, MA 02215, USAWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02139, USA; Vascular Biology Program and Department of Surgery, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy observed in human patients in vivo. Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase. These findings might help to explain the high level of resistance to therapy in cancer patients with minimal residual disease in regions of the lung that remain functionally aerated and mobile, in addition to providing an experimental model to study cancer persister cells and mechanisms of tumor dormancy in vitro. : Hassell et al. demonstrate that, when human lung cancer cells are grown within organ-on-a-chip culture devices that mimic lung structure and function, tumor cells recapitulate tumor growth and invasion patterns, as well as responses to therapy, observed in human patients. They also discover that breathing motions influence these responses. Keywords: lung cancer, microfluidic, organ-on-chip, invasion, persister cell, tyrosine kinase inhibitor, EGFR inhibitor, mechanical, chemotherapy, mechanobiologyhttp://www.sciencedirect.com/science/article/pii/S2211124717313311 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bryan A. Hassell Girija Goyal Esak Lee Alexandra Sontheimer-Phelps Oren Levy Christopher S. Chen Donald E. Ingber |
spellingShingle |
Bryan A. Hassell Girija Goyal Esak Lee Alexandra Sontheimer-Phelps Oren Levy Christopher S. Chen Donald E. Ingber Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro Cell Reports |
author_facet |
Bryan A. Hassell Girija Goyal Esak Lee Alexandra Sontheimer-Phelps Oren Levy Christopher S. Chen Donald E. Ingber |
author_sort |
Bryan A. Hassell |
title |
Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro |
title_short |
Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro |
title_full |
Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro |
title_fullStr |
Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro |
title_full_unstemmed |
Human Organ Chip Models Recapitulate Orthotopic Lung Cancer Growth, Therapeutic Responses, and Tumor Dormancy In Vitro |
title_sort |
human organ chip models recapitulate orthotopic lung cancer growth, therapeutic responses, and tumor dormancy in vitro |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-10-01 |
description |
Summary: Here, we show that microfluidic organ-on-a-chip (organ chip) cell culture technology can be used to create in vitro human orthotopic models of non-small-cell lung cancer (NSCLC) that recapitulate organ microenvironment-specific cancer growth, tumor dormancy, and responses to tyrosine kinase inhibitor (TKI) therapy observed in human patients in vivo. Use of the mechanical actuation functionalities of this technology revealed a previously unknown sensitivity of lung cancer cell growth, invasion, and TKI therapeutic responses to physical cues associated with breathing motions, which appear to be mediated by changes in signaling through epidermal growth factor receptor (EGFR) and MET protein kinase. These findings might help to explain the high level of resistance to therapy in cancer patients with minimal residual disease in regions of the lung that remain functionally aerated and mobile, in addition to providing an experimental model to study cancer persister cells and mechanisms of tumor dormancy in vitro. : Hassell et al. demonstrate that, when human lung cancer cells are grown within organ-on-a-chip culture devices that mimic lung structure and function, tumor cells recapitulate tumor growth and invasion patterns, as well as responses to therapy, observed in human patients. They also discover that breathing motions influence these responses. Keywords: lung cancer, microfluidic, organ-on-chip, invasion, persister cell, tyrosine kinase inhibitor, EGFR inhibitor, mechanical, chemotherapy, mechanobiology |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717313311 |
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