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.
Highlights
Cancer tissues are highly complex and heterogeneous structures, consisting of blood vessels, extracellular matrix and multiple cell types, such as cancer cells, fibroblasts, vascular, and immune cells[1]
We engineered a microfluidic system to evaluate the effect of shear stress on a model system to partially represent the microenvironment of esophageal pathologies and report the effects of fluid flow on the phenotypic plasticity of these cancer cells, in effort to demonstrate the efficacy of bioengineered systems as novel in vitro cancer models
In the Stokes flow, average wall shear stress at the middle of the channel is calculated as 1.44 × 10−5 Pa. Mechanical microenvironmental factors such as flow-induced shear stress can modulate the physiology of cancer cells[25]
Summary
Induces Phenotypic Plasticity of Esophageal Cancer Cells Under Flow received: 21 June 2016 accepted: 07 November 2016 Published: 02 December 2016. Changes in the physical conditions of the tumor microenvironment, driven by elevated tissue growth, proliferation of tumor cells and angiogenesis, may introduce exposure of laminar fluid flow and flow-driven shear stress on cancer tissue, which affects the level of heterogeneity and plasticity of cancer cells[2,3,4,5,6]. We engineered a microfluidic system to evaluate the effect of shear stress on a model system to partially represent the microenvironment of esophageal pathologies and report the effects of fluid flow on the phenotypic plasticity of these cancer cells, in effort to demonstrate the efficacy of bioengineered systems as novel in vitro cancer models
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