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Int J Mol Sci. 2017 Sep 28;18(10). pii: E2066. doi: 10.3390/ijms18102066.

Challenges for Super-Resolution Localization Microscopy and Biomolecular Fluorescent Nano-Probing in Cancer Research.

Author information

1
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. hausmann@kip.uni-heidelberg.de.
2
Laboratory of Molecular and Cellular Cancer Biology, Faculty of Medicine, Bar-Ilan University, 8 Henrietta Szold ST, Safed 1311502, Israel. natasa.ilic@biu.ac.il.
3
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. goetz.pilarczyk@kip.uni-heidelberg.de.
4
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. jin-ho.lee@kip.uni-heidelberg.de.
5
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. abiramy_l@hotmail.com.
6
Laboratory of Molecular and Cellular Cancer Biology, Faculty of Medicine, Bar-Ilan University, 8 Henrietta Szold ST, Safed 1311502, Israel. aurorapaola.borroni@gmail.com.
7
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. krufczik@kip.uni-heidelberg.de.
8
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. f.theda@gmx.de.
9
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. nadine.waltrich@googlemail.com.
10
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. f.bestvater@dkfz.de.
11
Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany. hilden@kip.uni-heidelberg.de.
12
Department of Radiation Oncology, Universitätsmedizin Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 3-5, 68159 Mannheim, Germany. hilden@kip.uni-heidelberg.de.
13
Institute of Molecular Biology, Ackermannweg 4, 55128 Mainz, Germany. C.Cremer@imb-mainz.de.
14
Laboratory of Molecular and Cellular Cancer Biology, Faculty of Medicine, Bar-Ilan University, 8 Henrietta Szold ST, Safed 1311502, Israel. michael.blank@biu.ac.il.

Abstract

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. By means of a tool-box of fluorescent antibodies, green fluorescent protein (GFP) tagging, or specific oligonucleotides, we present tumor relevant re-arrangements of Erb-receptors in membranes, 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.

KEYWORDS:

Smurf2; cancer research; chromatin organization; chromatin radiation response; fluorescent nano-probes; receptor conformation changes; super-resolution localization microscopy; γ-H2AX phosphorylation sites

PMID:
28956810
PMCID:
PMC5666748
DOI:
10.3390/ijms18102066
[Indexed for MEDLINE]
Free PMC Article

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