Fidler, I.J., Nat. Rev. Cancer (2003)

Road map to cancer metastasis

Thierry, J.P., Nat. Rev. Cancer (2002)

Epithelial-to-mesenchymal transition: explaining cancer invasion and metastasis

Classification of migration modes

Wolf et al., Nat. Cell Biol. (2007); Friedl & Gilmour, Nat. Rev. Mol. Cell Biol. (2009); Friedl & Wolf, J. Cell Biol. (2010)

The multiscale tuning model

Friedl & Wolf, J. Cell Biol. 2010

Collective cell migration

MT1-MMP is required for collective invasion in 3D collagen lattices

F-actin Col2 ¾ DAPI Reflection

siCtrl

siMT1

Wolf et al., Nat. Cell Biol. (2007)

Micropatterning

*

I / II

Pseudopod elongation,adhesion,

force generation

III

Focalizedproteolysis

IV

Fibrerealignment

V

Release ofmicrotrack

10-15 µm

Movingfibres

***

Sustainedcleavage

Zones of physicalresistance

Proteolyticmicrotrack

Individual and collective cancer cell invasion in 3D ECM

F-actinß1 integrinMT1-MMPCollagenolysis

Single-cell migration

Macropatterning I

Microtrack formation

II

Proteolysis of sheet-like interface Track widening (macrotrack)

Collective cell invasion

Collectiveinvasion /invasivegrowth

Friedl & Wolf, Cancer Res. (2008)

Drop-on Spheroid injection

Variants of the dorsal skin-fold chamber model