Leiden University Scholarly Publications

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Le Dévédec, S.E. (2010)

Adhesion signaling and tumor cell migration : a systems microscopy approach towards understanding cancer metastasis

Doctoral Thesis
Tumor cell migration and invasion are essential steps in cancer metastasis. Better understanding of the molecular mechanisms and function of the individual proteins affecting this behaviour is essential to define potential novel drug targets to combat cancer. In general, cells in a normal tissue environment are attached to the extra-cellular matrix (ECM) and to each others. The interactions with the ECM are mediated through integrin adhesion receptors. Matrix adhesions are the physical link between the ECM and the actin cytoskeleton and are important for survival, proliferation, differentiation and migration. These cytoplasmic structures are composed of various signaling (phosphatases and kinases) and structural proteins that form the so-called __integrin-adhesome__. The spatial and temporal regulations of these components determine the type of matrix adhesion, their behaviour and finally the fate of the cell. For instance, resting cells such as renal epithelial cells show enlarged...Show moreTumor cell migration and invasion are essential steps in cancer metastasis. Better understanding of the molecular mechanisms and function of the individual proteins affecting this behaviour is essential to define potential novel drug targets to combat cancer. In general, cells in a normal tissue environment are attached to the extra-cellular matrix (ECM) and to each others. The interactions with the ECM are mediated through integrin adhesion receptors. Matrix adhesions are the physical link between the ECM and the actin cytoskeleton and are important for survival, proliferation, differentiation and migration. These cytoplasmic structures are composed of various signaling (phosphatases and kinases) and structural proteins that form the so-called __integrin-adhesome__. The spatial and temporal regulations of these components determine the type of matrix adhesion, their behaviour and finally the fate of the cell. For instance, resting cells such as renal epithelial cells show enlarged and stable focal adhesions as well as tight cell-cell contacts. In contrast, tumor cells which are able to invade and metastasize, lose their interactions with adjacent cells and show fast, small and highly dynamic matrix adhesions. In this thesis, we set up technologies and investigated the molecular mechanisms of the matrix adhesions dynamics in relation to tumor cell behaviour both in vitro and in vivo situation.Show less
Cancer
Dynamic imaging
Focal adhesions
Light microscopy
Metastasis
All authors
Le Dévédec, S.E.
Supervisor
Water, B. van de
Committee
Danhof, M.; Dijke, P. ten; Kuijper, J.; Tanke, H.; Verschure, P.J.
Qualification
Doctor (dr.)
Awarding Institution
Leiden/Amsterdam Center for Drug Research (LACDR), Faculty of Science, Leiden University
Date
2010-02-17
ISBN (print)
9789090250977

Funding

Sponsorship
The publication of the thesis was financially supported by the Leiden/Amsterdam Center for Drug Research, Nikon Instruments Europe BV and the Stichting tot Bevordering van de Electronenmicroscopie in Nederland (SEN).