Event Abstract Back to Event Culture dimensionality controls CD44 alternative splicing Cristiana Branco Da Cunha1, 2, 3, 4, Darinka D. Klumpers1, 2, 5, Sandeep T. Koshy1, 2, 6, James C. Weaver2, Ovijit Chaudhuri7, Raquel Seruca3, Fátima Carneiro3, 4, Pedro L. Granja3, 8, 9 and David J. Mooney1, 2 1 Harvard University, School of Engineering and Applied Sciences, United States 2 Harvard University, Wyss Institute for Biologically Inspired Engineering, United States 3 Universidade do Porto, Instituto de Investigação e Inovação em Saúde (i3S), Portugal 4 Universidade do Porto, Faculdade de Medicina/Hospital S. João, Portugal 5 VU University Medical Center, Department Orthopedic Surgery, Research Institute MOVE, Netherlands 6 Harvard University-MIT, Division of Health Sciences and Technology, United States 7 Stanford University, Department of Mechanical Engineering, United States 8 Faculdade de Engenharia da Universidade do Porto, Departamento de Engenharia Metalúrgica e Materiais, Portugal 9 Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Portugal CD44 and its alternative spliced variants have been broadly associated with cancer, from resistance to oxidative stress to metastatic behavior. In the context of gastric cancer (GC) we have previously shown that de novo expression of CD44 variant 6 (CD44v6) accompanies malignant progression. Two-dimensional (2D) cell culture is commonly used to study cancer in vitro, but fails to mimic key architectural and physical features of the tumor microenvironment. This study determined how more physiologically relevant three-dimensional (3D) culture impacts CD44 alternative splicing in epithelial GC cells. In 3D culture, GC cells gradually lost expression of the standard CD44 isoform (CD44s), while simultaneously gaining CD44v6 expression that was virtually absent in 2D monolayers. This switch in CD44 spliced isoforms was reversible, accelerated by nutrient shortage and delayed with lower initial cell densities, suggesting that it is a stress-induced response. Loss of CD44s in 3D culture was further shown to be dependent on the matrix mechanical properties and accompanied by the upregulation of key epithelial-mesenchymal transition (EMT) markers, such as SNAIL and ZEB1, along with several genes involved in aberrant metabolic pathways, cellular stress, angiogenesis and antisenescense cellular programs. Human gastric premalignant and malignant lesions revealed that 3D cultures, but not 2D monolayers, were able to capture aberrant CD44 splicing patterns observed in vivo. Altogether, these findings suggest that cells modulate CD44 expression in response to culture dimensionality and physical cues, and could translate into clinical strategies to locally modulate CD44 expression in GC, the 4th most common cancer in the world. Keywords: Extracellular Matrix, Clinical relevance, mechanical property, matrix-cell interaction Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials and cellular signaling Citation: Branco Da Cunha C, Klumpers DD, Koshy ST, Weaver JC, Chaudhuri O, Seruca R, Carneiro F, Granja PL and Mooney DJ (2016). Culture dimensionality controls CD44 alternative splicing. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00598 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Cristiana Branco Da Cunha Darinka D Klumpers Sandeep T Koshy James C Weaver Ovijit Chaudhuri Raquel Seruca Fátima Carneiro Pedro L Granja David J Mooney Google Cristiana Branco Da Cunha Darinka D Klumpers Sandeep T Koshy James C Weaver Ovijit Chaudhuri Raquel Seruca Fátima Carneiro Pedro L Granja David J Mooney Google Scholar Cristiana Branco Da Cunha Darinka D Klumpers Sandeep T Koshy James C Weaver Ovijit Chaudhuri Raquel Seruca Fátima Carneiro Pedro L Granja David J Mooney PubMed Cristiana Branco Da Cunha Darinka D Klumpers Sandeep T Koshy James C Weaver Ovijit Chaudhuri Raquel Seruca Fátima Carneiro Pedro L Granja David J Mooney Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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