Challenges for super-resolution localization microscopy and biomolecular fluorescent nano-probing in cancer research

Michael Hausmann, Nataŝa Ilić, Götz Pilarczyk, Jin Ho Lee, Abiramy Logeswaran, Aurora Paola Borroni, Matthias Krufczik, Franziska Theda, Nadine Waltrich, Felix Bestvater, Georg Hildenbrand, Christoph Cremer, Michael Blank

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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. 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.

Original languageEnglish
Article number2066
JournalInternational Journal of Molecular Sciences
Volume18
Issue number10
DOIs
StatePublished - 28 Sep 2017

Bibliographical note

Publisher Copyright:
© 2017 by the authors.

Keywords

  • Cancer research
  • Chromatin organization
  • Chromatin radiation response
  • Fluorescent nano-probes
  • Receptor conformation changes
  • Smurf2
  • Super-resolution localization microscopy
  • γ-H2AX phosphorylation sites

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