Integrated Microfluidic Platform with Multiple Functions To Probe Tumor-Endothelial Cell Interaction.

Interaction between tumor and endothelial cells could affect tumor growth and progression and induce drug resistance during cancer therapy. Investigation of tumor-endothelial cell interaction involves cell coculture, protein detection, and analysis of drug metabolites, which are complicated and time-consuming. In this work, we present an integrated microfluidic device with three individual components (cell coculture component, protein detection component, and pretreatment component for drug metabolites) to probe the interaction between tumor and endothelial cells. Cocultured cervical carcinoma cells (CaSki cells) and human umbilical vein endothelial cells (HUVECs) show higher resistance to chemotherapeutic agents than single-cultured cells, indicated by higher cell viability, increased expression of angiogenic proteins, and elevated level of paclitaxel metabolites under coculture conditions. This integrated microfluidic platform with multiple functions facilitates understanding of the interaction between tumor and endothelial cells, and it may become a promising tool for drug screening within an engineered tumor microenvironment.

[1]  Qiang Z Yu,et al.  Apoptosis, autophagy, necroptosis, and cancer metastasis , 2015, Molecular Cancer.

[2]  L. Ellis,et al.  Endothelial cells promote the colorectal cancer stem cell phenotype through a soluble form of Jagged-1. , 2013, Cancer cell.

[3]  B. Vainer,et al.  TNF Receptor-2 Facilitates an Immunosuppressive Microenvironment in the Liver to Promote the Colonization and Growth of Hepatic Metastases. , 2015, Cancer research.

[4]  R. Ransohoff,et al.  Inflammatory reaction after traumatic brain injury: therapeutic potential of targeting cell-cell communication by chemokines. , 2015, Trends in pharmacological sciences.

[5]  Achilleas S. Frangakis,et al.  Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs , 2012, Nature Cell Biology.

[6]  D. Zhao,et al.  A facile soft-template synthesis of mesoporous polymeric and carbonaceous nanospheres , 2013, Nature Communications.

[7]  I. Lavi,et al.  Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients , 2008, Acta oncologica.

[8]  Matthew Greenwood,et al.  Anti-apoptosis and cell survival: a review. , 2011, Biochimica et biophysica acta.

[9]  Li Wang,et al.  Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells , 2014, Scientific Reports.

[10]  Qi Zhang,et al.  Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis. , 2016, Cancer research.

[11]  Peng Li,et al.  Controlling cell–cell interactions using surface acoustic waves , 2014, Proceedings of the National Academy of Sciences.

[12]  N. Salomonis,et al.  Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma , 2015, Cell Death and Disease.

[13]  M. Gottesman,et al.  Mathematical Modeling Reveals That Changes to Local Cell Density Dynamically Modulate Baseline Variations in Cell Growth and Drug Response. , 2016, Cancer research.

[14]  C. Nathan,et al.  Beyond oxidative stress: an immunologist's guide to reactive oxygen species , 2013, Nature Reviews Immunology.

[15]  Xuexia Lin,et al.  Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system , 2015, Scientific Reports.

[16]  D. Cheresh,et al.  Pathophysiological consequences of VEGF-induced vascular permeability , 2005, Nature.

[17]  Yihai Cao,et al.  PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells , 2011, Nature Medicine.

[18]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[19]  Christian Siltanen,et al.  Microfluidic co-cultures with hydrogel-based ligand trap to study paracrine signals giving rise to cancer drug resistance. , 2015, Lab on a chip.

[20]  Haifang Li,et al.  Cell signaling analysis by mass spectrometry under coculture conditions on an integrated microfluidic device. , 2011, Analytical chemistry.

[21]  Jinyi Wang,et al.  On-Chip Construction of Liver Lobule-like Microtissue and Its Application for Adverse Drug Reaction Assay. , 2016, Analytical chemistry.

[22]  Jin-Ming Lin,et al.  Determination of cell metabolite VEGF₁₆₅ and dynamic analysis of protein-DNA interactions by combination of microfluidic technique and luminescent switch-on probe. , 2016, Biosensors & bioelectronics.

[23]  Qiushui Chen,et al.  Biochemical analysis on microfluidic chips , 2016 .

[24]  Xiannian Zhang,et al.  Microfluidic Device for Studying Controllable Hydrodynamic Flow Induced Cellular Responses. , 2017, Analytical chemistry.

[25]  G. Dubini,et al.  A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone. , 2014, Biomaterials.

[26]  Tianbao Li,et al.  Monitoring tumor response to anticancer drugs using stable three-dimensional culture in a recyclable microfluidic platform. , 2015, Analytical chemistry.

[27]  Deyu Li,et al.  A microfluidic cell co-culture platform with a liquid fluorocarbon separator , 2014, Biomedical microdevices.

[28]  P. LaViolette,et al.  CXM: a new tool for mapping breast cancer risk in the tumor microenvironment. , 2014, Cancer research.

[29]  Guoqing Hu,et al.  Nonspecific Organelle-Targeting Strategy with Core-Shell Nanoparticles of Varied Lipid Components/Ratios. , 2016, Analytical chemistry.

[30]  Alexander Revzin,et al.  Functional imaging of neuron–astrocyte interactions in a compartmentalized microfluidic device , 2016, Microsystems & Nanoengineering.

[31]  Jin-Ming Lin,et al.  An in vitro liver model on microfluidic device for analysis of capecitabine metabolite using mass spectrometer as detector. , 2015, Biosensors & bioelectronics.

[32]  Mengsu Yang,et al.  Microfluidic Platform for Studying Chemotaxis of Adhesive Cells Revealed a Gradient-Dependent Migration and Acceleration of Cancer Stem Cells. , 2015, Analytical chemistry.

[33]  Haifang Li,et al.  Strategy for signaling molecule detection by using an integrated microfluidic device coupled with mass spectrometry to study cell-to-cell communication. , 2013, Analytical chemistry.

[34]  S. Hayward,et al.  Stretching Fibroblasts Remodels Fibronectin and Alters Cancer Cell Migration , 2015, Scientific Reports.