Understanding molecular interactions and regulatory mechanisms in tumor initiation, progression, and treatment response are key requirements towards advanced cancer diagnosis and novel treatment procedures in personalized medicine. Beyond decoding the gene expression, malfunctioning and cancer-related epigenetic pathways, investigations of the spatial receptor arrangements in membranes and genome organization in cell nuclei, on the nano-scale, contribute to elucidating complex molecular mechanisms in cells and tissues. By these means, the correlation between cell function and spatial organization of molecules or molecular complexes can be studied, with respect to carcinogenesis, tumor sensitivity or tumor resistance to anticancer therapies, like radiation or antibody treatment. Here, we present several new applications for bio-molecular nano-probes and super-resolution, laser fluorescence localization microscopy and their potential in life sciences, especially in biomedical and cancer research. Bymeans of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors inmembranes, spatial organization of Smad specific ubiquitin protein ligase 2 (Smurf2) in the cytosol, tumor cell characteristic heterochromatin organization, and molecular re-arrangements induced by radiation or antibody treatment. The main purpose of this article is to demonstrate how nano-scaled distance measurements between bio-molecules, tagged by appropriate nano-probes, can be applied to elucidate structures and conformations of molecular complexes which are characteristic of tumorigenesis and treatment responses. These applications open new avenues towards a better interpretation of the spatial organization and treatment responses of functionally relevant molecules, at the single cell level, in normal and cancer cells, offering new potentials for individualized medicine.
|Journal||International Journal of Molecular Sciences|
|State||Published - 28 Sep 2017|
Bibliographical noteFunding Information:
Acknowledgments: Michael Hausmann and Christoph Cremer thank for the financial support of the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (FKZ: SR/StSch/INT 3610S30015). Data curation and archiving has been supported to Michael Hausmann by the Helmholtz Portfolio Extension Large Scale Data Management and Analysis with contributions from the Data Life Cycle Lab Key Technologies and the Data Services Integration Team. Furthermore, the support of the Innovation Fond “Frontier” of the Heidelberg University within the excellence initiative of the Deutsche Forschungsgemeinschaft (DFG) to Georg Hildenbrand and Michael Hausmann as well as the drug support of Roche Diagnostics GmbH are gratefully acknowledged. The financial support by Deutsche Forschungsgemeinschaft and Ruprecht-Karls-Universität Heidelberg within the funding program Open Access Publishing is gratefully acknowledged. Michael Blank gratefully acknowledges the support of Marie-Curie CIG, FP-7-People (#612816), ICRF (#00636) and Harry B. Helmsley Charitable Trust. He also thanks for the financial support Morris and Sasson Dayan Family Foundation. The authors thank Margund Bach, Maksym Gachkivskyi, Jan Neumann, Jutta Schwarz-Finsterle, Patrick Müller, Eberhard Schmitt, and Michael Stuhlmüller (all members of Kirchhoff-Institute for Physics, University of Heidelberg) as well as Florian Schock (Institute for Molecular Biology, Mainz) for their continuous help and fruitful discussions. Finally, the authors thank Corinna-Cornelia Seegler-Sandbanck, European Institute for Feasibility Studies, Strasburg (Um.), Germany, for bringing light into dark moments of science.
© 2017 by the authors.
- Cancer research
- Chromatin organization
- Chromatin radiation response
- Fluorescent nano-probes
- Receptor conformation changes
- Super-resolution localization microscopy
- γ-H2AX phosphorylation sites