title: Interfacial geometry dictates cancer cell tumorigenicity.
abstract: Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Junmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Amr A
authors.initials: AA
authors.lastname: Abdeen
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Wycislo
authors.affiliation: Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Fan
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Kristopher A
authors.initials: KA
authors.lastname: Kilian
mesh_terms: D063646:Carcinogenesis / Q000473:pathology*; D045744:Cell Line, Tumor; D048430:Cell Shape; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology; D015398:Signal Transduction; D059016:Tumor Microenvironment