title: Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines.
abstract: Cancer is characterized by cell heterogeneity and the development of 3D in vitro assays that can distinguish more invasive or migratory phenotypes could enhance diagnosis or drug discovery. 3D collagen scaffolds have been used to develop analogues of complex tissues in vitro and are suited to routine biochemical and immunological assays. We sought to increase 3D model tractability and modulate the migration rate of seeded cells using an ice-templating technique to create either directional/anisotropic or non-directional/isotropic porous architectures within cross-linked collagen scaffolds. Anisotropic scaffolds supported the enhanced migration of an invasive breast cancer cell line MDA-MB-231 with an altered spatial distribution of proliferative cells in contrast to invasive MDA-MB-468 and non-invasive MCF-7 cells lines. In addition, MDA-MB-468 showed increased migration upon epithelial-to-mesenchymal transition (EMT) in anisotropic scaffolds. The provision of controlled architecture in this system may act both to increase assay robustness and as a tuneable parameter to capture detection of a migrated population within a set time, with consequences for primary tumour migration analysis. The separation of invasive clones from a cancer biomass with in vitro platforms could enhance drug development and diagnosis testing by contributing assay metrics including migration rate, as well as modelling cell-cell and cell-matrix interaction in a system compatible with routine histopathological testing.
authors.affiliation: Cambridge Centre for Medical Materials, Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Campbell
authors.affiliation: Cambridge Centre for Medical Materials, Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK. Electronic address: ah492@cam.ac.uk.
authors.forename: Anke
authors.initials: A
authors.lastname: Husmann
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hume
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Watson
authors.affiliation: Cambridge Centre for Medical Materials, Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Cameron
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry*; D004867:Equipment Design; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D066330:Printing, Three-Dimensional; D046888:Tissue Array Analysis / Q000295:instrumentation*; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D003094:Collagen
keywords: Breast cancer; Collagen 1; Ice-templating technique; Invasion; Scaffold architecture; Three dimensional migration