title: A biomaterial model of tumor stromal microenvironment promotes mesenchymal morphology but not epithelial to mesenchymal transition in epithelial cells.
abstract: The stromal tissue surrounding most carcinomas is comprised of an extracellular matrix densely packed with collagen-I fibers, which are often highly aligned in metastatic disease. Here we developed an in vitro model to test the effect of an aligned fibrous environment on cancer cell morphology and behavior, independent of collagen ligand presentation. We grew cells on a biomimetic surface of aligned electrospun poly-l-lactic acid (PLLA) fibers and then examined the effect of this environment on growth rate, morphology, cytoskeletal organization, biochemical and genetic markers of epithelial to mesenchymal transition (EMT), cell surface adhesion, and cell migration. We grew a phenotypically normal breast epithelial cell line (MCF10A) and an invasive breast cancer cell line (MDA-MB-231) on three different substrates: typical flat culture surface (glass or plastic), flat PLLA (glass coated with PLLA) or electrospun PLLA fibers. Cells of both types adopted a more mesenchymal morphology when grown on PLLA fibers, and this effect was exaggerated in the more metastatic-like MDA-MB-231 cells. However, neither cell type underwent the changes in gene expression indicative of EMT despite the changes in cell shape, nor did they exhibit the decreased adhesive strength or increased migration typical of metastatic cells. These results suggest that changes in cell morphology alone do not promote a more mesenchymal phenotype and consequently that the aligned fibrous environment surrounding epithelial cancers may not promote EMT solely through topographical cues.
authors: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
authors: Joshua S
authors: JS
authors: McLane
authors: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
authors: Christopher J
authors: CJ
authors: Rivet
authors: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
authors: Ryan J
authors: RJ
authors: Gilbert
authors: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA. Electronic address: ligonl@rpi.edu.
authors: Lee A
authors: LA
authors: Ligon
mesh_terms: D000199:Actins / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D024022:Fibrillar Collagens / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D008648:Mesoderm / Q000187:drug effects / Q000473:pathology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D024022:Fibrillar Collagens; D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Breast cancer; Electrospun fibers; Epithelial cells; Epithelial to mesenchymal transition; Topography