Date

2017

Document Type

Thesis

Degree

Master of Science

Department

Bioengineering

First Adviser

Bucets, Javier

Abstract

Tumor progression fate relies on the cell competition between tumorous cells and the surrounding regular cells. Studies on the Drosophila wing imaginal disc illustrate that cell competition can act either as a tumor suppressing or as a tumor promoting mechanism. However, how cell competition alters its role in tumor development via underlying molecular mechanisms as well as the role played by mechanical effects is still poorly understood. Here we study the role of cell competition in the early stage of tumor progression, using a simulation code of epithelial tissue (TiFoSi), which allows to include feedback between tissue growth, mechanics and gene regulation. Cells with inactivating mutations of tumor suppressor gene scrib always show hallmarks of carcinomas3,6. Multiple simulations show: 1) the clone of scrib mutant cells can be outcompeted and eliminated from the tissue, when surrounded by a wild-type tissue, even though they can proliferate infinitely on their own. 2) the initial size of the mutant clone can escape from the fate of elimination and expand, by protecting the inside cells from the range of cell competition, depending on the size of the initial tumorous clone. The results fits with experimental results and sheds light on how and why cell competition regulates tumor progression.

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