Adhesion signaling and tumor cell migration:
a systems microscopy approach towards understanding cancer metastasis
Sylvia Le Dévédec
Adhesion signaling and tumor cell migration: a systems microscopy approach towards understanding cancer metastasis
Sylvia Le Dévédec February 2010
ISBN: 978-90-9025097-7
©2009, Sylvia Le Dévédec. All right reserved. No part of this thesis may be reproduced or transmitted in any form, by any means, electronic or mechanical, without prior written permission of the author.
Cover: adapted from ‘Locomotion humaine´ (1870) by the French photograph Etienne-Jules Marey (1830-1904), design by Hagen Rißmann
Printed by Wöhrmann Print Service, Zutphen, The Netherlands
Adhesion signaling and tumor cell migration:
a systems microscopy approach towards understanding cancer metastasis
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties
te verdedigen op woensdag 17 Februari 2010 klokke 15.00 uur
door
Sylvia Emmanuelle Le Dévédec geboren te Ploemeur, Frankrijk
in 1976
PROMOTION COMMITTEE
Promotor: Prof. Dr. B. van de Water LACDR, Leiden Overige leden: Prof. Dr. M. Danhof LACDR, Leiden Prof. Dr. P. ten Dijke LUMC, Leiden Prof. Dr. J. Kuijper LACDR, Leiden
Prof. Dr. H. Tanke LUMC, Leiden
Dr. P.J. Verschure UvA, Amsterdam
The investigations described in this thesis were performed at the Division of Toxicology of the Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, the Netherlands.
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).
Pour Gwendoline
TABLE OF CONTENTS
Chapter 1: 9
General introduction: matrix adhesions, cell migration and breast cancer
Chapter 2: 29
Focal Adhesion Kinase (FAK) inhibition as a potential strategy for anticancer therapies
Chapter 3: 45 A systems microscopy approach towards understanding tumor cell
migration: quantitative multiparameter evaluation of cellular and molecular dynamics
Chapter 4: 81
The residence time of Focal Adhesion Kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size and integrin ligand density
Chapter 5: 111
An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2-/-γc-/- mouse
Chapter 6: 133
Two-photon intravital multi-color imaging combined with inducible gene expression to distinguish metastatic behaviour of breast cancer cells in vivo
Chapter 7: 155
Scaffold protein paxillin serine 178 phosphorylation determines mammary tumor cell migration and metastasis formation through regulating EGFR expression
Chapter 8: 179
Summary and discussion Miscellaneous
Samenvatting (Dutch summary) 197
List of abbreviations 201
Curriculum vitae 203
List of publications 205
Acknowledgments 207
