This document discusses approaches to diagnosing and treating tumors through physics. It summarizes research on the spread of tumor cells through invasion and migration in tissues and blood vessels to form secondary tumors. Graphs and images show mechanisms of cell crawling, the balance of forces during invasion, strain energy in invaded cells, and mean squared displacement measurements. Automatic analysis of invasion profiles can classify tumor cell lines. Gene expression profiles correlate with invasiveness and processes like matrix adhesion, deadhesion, and focal adhesion. Cell invasion assays study the effects of drugs and genes on the metastatic mechanism.

1. Physikalische Ansätze zur Diagnostik
und Therapie von Tumoren
Ben Fabry
Institut für Kondensierte Materie
Department für Physik
Zentrum für Physikalisch‐Medizinische Technik

2. Metastasis
primary tumor
spread of tumor cells
invasion
transendothelial migration
adhesion transport through
blood or lymph
vessels
transendothelial
migration
invasion
secondary tumor

3. Cell crawling and migration in 2-D
• CSK dynamics
• adhesion
• de-adhesion
Crawling Neutrophil
Chasing a Bacterium
(D Rogers)
(Alberts B. et al., Molecular Biology of the Cell)
Resisting forces of the surroundings = zero

7. Cell invasion is governed by a force balance
adhesion
receptor
de-adhesion
expression
bond-stability • protrusive forces
• traction forces
CSK-fluidity • CSK resistive forces
CSK-stiffness
CSK-dynamics enzymatic matrix • matrix resistive forces
degradation
matrix stiffness
2 µm

9. Strain energy around an invaded MDA-MB-231 cell
0 3.5 fJ/(10 µm)³

15. Mean Squared Displacement
5 Ballistic (slope 2)
10
4
10
Super-diffusive (slope 1.3)
3
10 Diffusive (slope 1)
MSD (µm2)
2
10
1
10
0
10 0 1 2 3
10 10 10 10
t (min)

16. Automatic measurement of the invasion profile

17. General characteristic features of the invasion profile

18. Classification of tumor cell lines

19. Gene expression profiles
non‐invasive invasive
MDA‐MB‐453
MDA‐MB‐231
MDA‐MB‐231
SW480
MS751
MCF‐7
786‐0
EJ‐28
A375
increased
average
decreased talin
laminin
urokinase Matrix Adhesion
positive correlation
integrin alpha 3
collagen IV Deadhesion
integrin alpha 5
integrin beta 3
Focal Adhesion
ADAM9 Matrix proteinases
TIMP1
integrin‐linked kinase (ILK)
vinculin
ADAM17
MMP14
calmodulin 3
microtubule‐associated protein (MAPRE2)
MMP2
negative correlation
keratin 18
Bauer et al, Int J Cancer 2007

22. Cell invasion assay
 Effect of drugs
 Influence of gene expression profile
 Cell types
 Understand the mechanism of metastasis formation
 Adhesion receptors
 Matrix proteinases
 Forces / cell contractility
 Cytoskeletal mechanics and dynamics