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BP: Fachverband Biologische Physik
BP 26: Multi-cellular systems and Physics of Cancer
BP 26.5: Vortrag
Mittwoch, 2. April 2014, 12:45–13:00, ZEU 250
A Distinct Intermolecular FasL Distance Triggers Either Apoptosis or Proliferation in Glioma and Pancreatic Cancer Cells — •Cornelia Monzel1, Thomas Kaindl1, Joel Beaudouin2,3, Susanne Kleber2, Marcin Teodorczyk2,4, Motomu Tanaka1,5, and Ana Martin-Villalba2 — 1Dept. of Physical Chemistry of Biosystems, Heidelberg University, Germany — 2Dept. of Molecular Neurobiology, DKFZ, Heidelberg, Germany — 3Dept. of Signal Transduction Biophysics, BioQuant, Heidelberg, Germany — 4Inst. for Microscopic Anatomy and Neurobiology, Mainz University, Germany — 5Inst. for Integrated Cell Materials Science, Kyoto University, Japan
The trimerized Fas receptor-ligand (Fas-FasL) interaction has long been described as inducer of apoptosis, but recent studies also suggest its critical role in proliferation or metastasis. In order to elucidate the mechanisms inducing cell death we designed quantitative cell surface models of supported lipid membranes displaying FasL at defined intermolecular distances (6-17 nm). Utilizing live cell imaging, we evaluated the reaction kinetics of cancer apoptosis. Intriguingly, in both glioma and pancreatic cancers an optimal ligand distance for the most effective apoptosis was found, which was accompanied by increased Fas-FasL aggregate formation. In contrast, when we transferred this membrane on microbeads injected into 3D tumors, pronounced proliferation and self-renewal in vivo and in vitro was observed. These findings demonstrate the significant impact of a distinct FasL distance, which results in opposite consequences in single- and multicellular sytems.