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2016.06 Pizza club - Marco

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Current concepts of mechanics in cancer research

Holle, Andrew W., Jennifer L. Young, and Joachim P. Spatz. "In vitro cancer cell–ECM interactions inform in vivo cancer treatment." Advanced drug delivery reviews (2015). http://dx.doi.org/10.1016/j.addr.2015.10.007

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2016.06 Pizza club - Marco

  1. 1. Current concepts of mechanics in cancer research Dipl.-ing. Marco Albrecht, PhD student at FSTC – Research Group: Systems Biology 15.06.2015 Pizza club marco.albrecht@uni.lu 1
  2. 2. The secret of the difference between in vivo phenomena and experimental 2D cell culture. HOLLE, ANDREW W., JENNIFER L. YOUNG, AND JOACHIM P. SPATZ. "IN VITRO CANCER CELL–ECM INTERACTIONS INFORM IN VIVO CANCER TREATMENT." ADVANCED DRUG DELIVERY REVIEWS (2015). 2
  3. 3. Some effects 3
  4. 4. Tumour mechanics PRESSURE AND STRESS 4
  5. 5. Tumour mechanics 5 The role of mechanical forces in tumor growth and therapy (2014) Jain et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors (2012).Stylianopoulos T1, Jain RK
  6. 6. Pressure and stress The role of mechanical forces in tumor growth and therapy (2014) Jain et al. Cell compression and matrix stiffening  Gen expression  Proliferation  Apoptosis  Invasiveness  ECM Blood and lymphatic vessel compression.  Reduction of oxygen, nutrient and drug delivery  Edema 6
  7. 7. Pressure and stress Solid stress: Mechanical forces exerted by non-fluid components accumulated within tumours - growth-induced stress remain after resection - externally applied stress due to surrounding tissue Fluid stress: - microvascular pressure (MVP) shear stress - interstitial fluid pressure (IFP) 7
  8. 8. Pressure and stress 8 Butcher, Darci T., Tamara Alliston, and Valerie M. Weaver. "A tense situation: forcing tumour progression." Nature Reviews Cancer 9.2 (2009): 108-122.
  9. 9. Tumour dynamics 9
  10. 10. Tumour dynamics 10 Book: Multi scale modelling of cancer (2012) Cristini and Lowengrub
  11. 11. Migration/Invasion 11
  12. 12. Cell migration Tozluoğlu, Melda, et al. "Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions." Nature cell biology 15.7 (2013): 751-762. 12
  13. 13. Cell migration 13
  14. 14. Cell migration ECM component orientation critical for migration direction Migration along reassembled collagen fiber “highways” Outwardly radiating collagen fiber patterns are observed in vivo and promote invasive behaviour 14
  15. 15. Cell mechanics and mechano signal transduction 15
  16. 16. Cell mechanics 16 Youtube: Jochen Guck - Alexander von Humboldt Professorship 2012 (EN) Otto, Oliver, et al. "Real-time deformability cytometry: on-the-fly cell mechanical phenotyping." Nature methods 12.3 (2015): 199-202. Guck, Jochen, et al. "Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence." Biophysical journal (2005)
  17. 17. Cell mechanics 17 Dupont, Sirio. "Role of YAP/TAZ in cell- matrix adhesion-mediated signalling and mechanotransduction." Experimental cell research (2015).
  18. 18. Mechano signal transduction 18 Butcher, Darci T., Tamara Alliston, and Valerie M. Weaver. "A tense situation: forcing tumour progression." Nature Reviews Cancer 9.2 (2009): 108-122. Traction force microscopy Dupont, Sirio. "Role of YAP/TAZ in cell- matrix adhesion-mediated signalling and mechanotransduction." Experimental cell research (2015).
  19. 19. Mechano signal transduction 19 Humphrey, Jay D., Eric R. Dufresne, and Martin A. Schwartz. "Mechanotransduction and extracellular matrix homeostasis." Nature Reviews Molecular Cell Biology 15.12 (2014): 802-812
  20. 20. Experimental perspective 20
  21. 21. Experimental platforms Cassereau, Luke, et al. "A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype." Journal of biotechnology 193 (2015) 21
  22. 22. Experimental platforms Stiffness control with natural biomaterials:  Collagen gels  hyaluronic acid  Matrigel Better stiffness control with artificial biomaterials:  Polyacrylamid (PA)  Polyethylene glycol (PEG)  Polydimethylsiloxane (PDMS) Steering via crosslinker to monomer ratio or photoinitiator systems 22 Kloxin, A., Anseth, K. S. (2009). Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science,
  23. 23. Imaging: Elastography and atomic force microscopy Kim, Woong, et al. "Application of Elastography for the Noninvasive Assessment of Biomechanics in Engineered Biomaterials and Tissues." Annals of Biomedical Engineering (2016): 1-20. 23
  24. 24. Gracias por su atención marco.albrecht@uni.lu Research group “Systems Biology” at the University of Luxembourg - FSTC Kiitos huomiota Grazie per l'attenzione Eskerrik asko zure arretagatik Nhờ sự quan tâm của bạn Obrigado pela sua atençãoMerci pour votre attention Danke für Ihre Aufmerksamkeit ขอบคุณสำหรับควำมสนใจของคุณ villmools Merci fir de Opmierksamkeet Benjamin Ahrenholz 24
  25. 25. The end 25

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