title: Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation.
abstract: A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Jessie S
authors.initials: JS
authors.lastname: Jeon
authors.affiliation: Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy; Cell and Tissue Engineering Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, 20161 Milan, Italy;
authors.forename: Simone
authors.initials: S
authors.lastname: Bersini
authors.affiliation: Cell and Tissue Engineering Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, 20161 Milan, Italy; PhD School in Life Sciences, Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy;
authors.forename: Mara
authors.initials: M
authors.lastname: Gilardi
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering, Politecnico di Milano, 20133 Milan, Italy;
authors.forename: Gabriele
authors.initials: G
authors.lastname: Dubini
authors.affiliation: Charles Stark Draper Laboratory, Cambridge, MA 02139; and.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Charest
authors.affiliation: Cell and Tissue Engineering Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Galeazzi, 20161 Milan, Italy; matteo.moretti@grupposandonato.it rdkamm@mit.edu.
authors.forename: Matteo
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 matteo.moretti@grupposandonato.it rdkamm@mit.edu.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000175:diagnosis*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D044085:Microfluidics / Q000379:methods*; D055806:Microvessels / Q000473:pathology*; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D000241:Adenosine
keywords: breast cancer; extravasation; metastasis; microenvironment; microfluidics