title: Three-dimensional chemotaxis-driven aggregation of tumor cells.
abstract: One of the most important steps in tumor progression involves the transformation from a differentiated epithelial phenotype to an aggressive, highly motile phenotype, where tumor cells invade neighboring tissues. Invasion can occur either by isolated mesenchymal cells or by aggregates that migrate collectively and do not lose completely the epithelial phenotype. Here, we show that, in a three-dimensional cancer cell culture, collective migration of cells eventually leads to aggregation in large clusters. We present quantitative measurements of cluster velocity, coalescence rates, and proliferation rates. These results cannot be explained in terms of random aggregation. Instead, a model of chemotaxis-driven aggregation - mediated by a diffusible attractant - is able to capture several quantitative aspects of our results. Experimental assays of chemotaxis towards culture conditioned media confirm this hypothesis. Theoretical and numerical results further suggest an important role for chemotactic-driven aggregation in spreading and survival of tumor cells.
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Puliafito
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Simone
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.|Edwin L. Steele Laboratory for Tumor Biology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Seano
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.|Department of Oncology, University of Turin, Turin 10060, Italy.
authors.forename: Paolo Armando
authors.initials: PA
authors.lastname: Gagliardi
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.|Department of Oncology, University of Turin, Turin 10060, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Di Blasio
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Chianale
authors.affiliation: Institute of Condensed Matter Physics and Complex Systems, Department of Applied Science and Technology, Polytechnic University of Turin, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy.|Human Genetics Foundation (HuGeF), Via Nizza 52, Torino, Italy.|Istituto Nazionale di Fisica Nucleare (INFN), Torino, Via Giuria 1, 10125 Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gamba
authors.affiliation: Candiolo Cancer Institute FPO-IRCCS, Candiolo, Turin, Italy.|Department of Oncology, University of Turin, Turin 10060, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Primo
authors.affiliation: Quantitative Life Sciences Unit, The Abdus Salam Center for Theoretical Physics (ICTP), Strada Costiera 11, I-34151 Trieste, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Celani
mesh_terms: D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological
chemical_list: D017077:Culture Media, Conditioned