title: An Engineered Breast Cancer Model on a Chip to Replicate ECM-Activation In Vitro during Tumor Progression.
abstract: In this work, a new model of breast cancer is proposed featuring both epithelial and stromal tissues arranged on a microfluidic chip. The main task of the work is the in vitro replication of the stromal activation during tumor epithelial invasion. The activation of tumor stroma and its morphological/compositional changes play a key role in tumor progression. Despite emerging evidences, to date the activation of tumor stroma in vitro has not been achieved yet. The tumor-on-chip proposed in this work is built in order to replicate the features of its native counterpart: multicellularity (tumor epithelial cell and stromal cell); 3D engineered stroma compartment composed of cell-assembled extracellular matrix (ECM); reliable 3D tumor architecture. During tumor epithelial invasion the stroma displayed an activation process at both cellular and ECM level. Similarly of what repeated in vivo, ECM remodeling is found in terms of hyaluronic acid and fibronectin overexpression in the stroma compartment. Furthermore, the cell-assembled ECM featuring the stromal tissue, allowed on-line monitoring of collagen remodeling during stroma activation process via real time multiphoton microscopy. Also, trafficking of macromolecules within the stromal compartment has been monitored in real time.
authors.affiliation: Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, P.le Tecchio 80, 80125, Napoli, Italy.|Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Napoli, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Gioiella
authors.affiliation: Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Urciuolo
authors.affiliation: Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Napoli, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Imparato
authors.affiliation: Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, P.le Tecchio 80, 80125, Napoli, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Brancato
authors.affiliation: Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, P.le Tecchio 80, 80125, Napoli, Italy.|Center for Advanced Biomaterials for Health Care@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Napoli, Italy.|Department of Chemical, Materials and Industrial Production (DICMAPI), University of Naples Federico II, P.le Tecchio 80, 80125, Napoli, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Netti
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D056656:Lab-On-A-Chip Devices; D044085:Microfluidics / Q000295:instrumentation; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D005353:Fibronectins; D006820:Hyaluronic Acid; D003094:Collagen
keywords: extracellular matrix; microfluidics; tumor microenvironment; tumor stroma; tumor-on-chip