Person:
Seano, Giorgio

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Seano

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Giorgio

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Seano, Giorgio

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    Publication
    Three-dimensional chemotaxis-driven aggregation of tumor cells
    (Nature Publishing Group, 2015) Puliafito, Alberto; De Simone, Alessandro; Seano, Giorgio; Gagliardi, Paolo Armando; Di Blasio, Laura; Chianale, Federica; Gamba, Andrea; Primo, Luca; Celani, Antonio
    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.
  • Publication
    Solid stress and elastic energy as measures of tumour mechanopathology
    (Springer Nature, 2016) Nia, Hadi; Jain, Rakesh; Liu, Hao; Seano, Giorgio; Datta, Meenal; Jones, Dennis; Rahbari, Nuh; Incio, Joao; Chauhan, Vikash; Jung, Keehoon; Martin, John D.; Askoxylakis, Vasileios; Padera, Timothy; Fukumura, Dai; Boucher, Yves; Hornicek, Francis; Grodzinsky, Alan J; Baish, James W; Munn, Lance
    Solid stress and tissue stiffness affect tumour growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumours, the measurement of solid stresses is challenging. Here, we show that two-dimensional spatial mappings of solid stress and the resulting elastic energy in excised or in situ tumours with arbitrary shapes and wide size ranges can be obtained via three distinct and quantitative techniques that rely on the measurement of tissue displacement after disruption of the confining structures. Application of these methods in models of primary tumours and metastasis revealed that: (i) solid stress depends on both cancer cells and their microenvironment; (ii) solid stress increases with tumour size; and (iii) mechanical confinement by the surrounding tissue significantly contributes to intratumoural solid stress. Further study of the genesis and consequences of solid stress, facilitated by the engineering principles presented here, may lead to significant discoveries and new therapies.