CARADI cancer irradiation project The interdisciplinary CARADI research project aims at modeling tumor dynamics under the action of irradiation and response of the immune system and includes microscopic mechanisms of biomolecule damage induced by ionic radiation. Scientists of different research fields at FIAS who are involved include W. Greiner , I. Mishustin, A. Solovyov, and the Systems Immunology Group of M. Meyer-Hermann. This preliminary information focuses on the cancer modelling part of the CARADI-project. The complete project description will be available soon. Agent-based simulation of Multicellular Tumour Spheroids Cancer is believed to develop from a single transformed cell belonging to the organism itself. Such a cell acquires different properties that allow it to proliferate arbitrarily often, thus circumventing for example the Hayflick limit dictated by telomer shortening. A malignant cell also develops strategies to avoid the attack of the immune system. For example the process of induced cell death is inhibited in tumour cells. They may reduce the presentation of markers on their surface, thus becoming invisible to the immune agents. The cells in a growing tumour have to be fed by nutrients like glucose and oxygen. The nutrients are provided by the neighbouring blood vessels and reach the cells internal to the tumour by diffusion. However, when overcoming a specific size, diffusion turns to become insufficient to keep the tumour cells living or even proliferating. The inner cells starve and die by necrosis. This gives rise to a necrotic core as observed in larger tumours before vascularisation. Vascularisation of the tumour, i.e. the development of new blood vessels that supply the tumour with nutrients, is a necessary prerequisite for the further development of the tumour. Figure 1: An agent-based simulation of the initial stage of an avascular tumour spheroid sourrounded by healthy tissue. Pov-ray rendering of the tumour in frontal view (left) and a cross section through the tumour middle (right). (by Harald Kempf) We aim at modelling the dynamical development of tumours in dependence on their tissue environment starting from the first malignant cell to the vascularised stage. This shall provide insight into the pathogenesis of cancer and allow to get knowledge of various mechanisms involved in the different steps of cancer development. Another hardly touched field of research is the emergence of metastasis, which involves several unknown parameters and is therefore challenging to be understood with theoretical methods. Important publications concerning the project: Meyer-Hermann, Michael E., 2007: Are T cells at the origin of B cell lymphomas? J. Theor. Biol. 244, 656-669 pdf Schaller, G., Meyer-Hermann, M., 2007: Epidermal homeostasis control in an off-lattice agent-based model. J. Theor. Biol. 247, 554-573 Schaller, G. and Meyer-Hermann, M., 2006: Continuum versus discrete model: a comparison for multicellular tumour spheroids. Phil. Trans. Roy. Soc. A 364, 1443-1464 Schaller, G., Meyer-Hermann, M., 2005: Multicellular tumor spheroid in an off-lattice Voronoi/Delaunay cell model. Phys. Rev. E 71, 051910-1-16. pdf For further information please contact Michael Meyer-Hermann Back

Harald Kempf. Frankfurt am Main, Germany  (2008)