title: Dynamic Microenvironment Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow.
abstract: Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress. We report the epithelial to hybrid epithelial/mesenchymal transition as a result of decreasing E-Cadherin and increasing N-Cadherin and vimentin expressions, higher clonogenicity and ALDH positive expression of cancer cells cultured in a dynamic microfluidic chip under laminar flow compared to the static culture condition. We also sought regulation of chemotherapeutics in cancer microenvironment towards phenotypic control of cancer cells. Such in vitro microfluidic system could potentially be used to monitor how the interstitial fluid dynamics affect cancer microenvironment and plasticity on a simple, highly controllable and inexpensive bioengineered platform.
authors.affiliation: Bio-Acoustic MEMS in Medicine Laboratory, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (by courtesy), Stanford School of Medicine, Palo Alto, California, 94304, USA.|Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, 35340, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Calibasi Kocal
authors.affiliation: Bio-Acoustic MEMS in Medicine Laboratory, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (by courtesy), Stanford School of Medicine, Palo Alto, California, 94304, USA.|Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, 35340, Turkey.
authors.forename: Sinan
authors.initials: S
authors.lastname: Güven
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, California, 94304, USA.
authors.forename: Kira
authors.initials: K
authors.lastname: Foygel
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts, 02115, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Goldman
authors.affiliation: Bio-Acoustic MEMS in Medicine Laboratory, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (by courtesy), Stanford School of Medicine, Palo Alto, California, 94304, USA.
authors.forename: Pu
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts, 02115, USA.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Bio-X Program, Stanford University School of Medicine, Palo Alto, California, 94304, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
authors.affiliation: Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, 35340, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Baskin
authors.affiliation: Bio-Acoustic MEMS in Medicine Laboratory, Canary Center at Stanford for Early Cancer Detection, Department of Radiology, Department of Electrical Engineering (by courtesy), Stanford School of Medicine, Palo Alto, California, 94304, USA.
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
mesh_terms: D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical; D059016:Tumor Microenvironment
chemical_list: D009363:Neoplasm Proteins