7th Annual Symposium
Physics of Cancer
Leipzig, Germany
October 4-6, 2016
Invited Talk
Mechanics of Cancer Cell Invasion in Vivo
Peter Friedl1,2
1The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number: 18-2 Houston, TX 77030, U.S.A.
2Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
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Single-cell or collective invasion results from coordination of cell shape, deformability and actin dynamics relative to the tissue environment. When monitored in vivo, using intravital multiphoton second and third harmonic generation and fluorescence microscopy, tissue microniches provide invasion-promoting tracks that enable collective migration along tracks of least resistance. As main routes, non-destructive contact-guidance is mediated by preformed multi-interface perimuscular, vascular and –neural tracks of 1D, 2D and 3D topography. 3D ultrastructural analysis reveals predefined tissue conduits (“highways”) of defined geometry, nanotropography and molecular composition as predominant routes of invasion by contact guidance combined with a cell “jamming” mechanism. Targeting of beta1/beta3 integrins induces profound plasticity of invasion, including collective and amoeboid single-cell dissemination, followed by enhanced systemic dissemination and micrometastasis. In conclusion, cancer invasion is maintained by physicochemical programs that balance cell-intrinsic adhesion and mechanocoupling with encountered physical space and molecular cues.
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