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.
Highlights
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
Any application of localization microscopy in cancer research, medical diagnoses and personalized medicine may be challenging in such a way that a point pattern obtained by loci information of individual molecules has to be translated into functionally relevant structures and organization principles
Localization microscopy is not just microscopic imaging with better resolution than so far established techniques
Summary
Recent progress in cancer research has established a consequential link between compromised genomic integrity, altered gene expression, impaired DNA damage response, and dysregulated membrane receptor activation and trafficking. These components form the main driving forces in carcinogenesis, and determine the therapeutic outcomes in many types of cancer [1,2,3,4,5,6,7,8,9,10,11,12,13]. This dearth of knowledge creates significant gaps in our understanding of the mechanisms operating in, and leading to, cancer initiation and progression, and the sensitivity of tumor cells to anticancer therapies, and impedes the design of novel, more efficient, therapeutic approaches to cure cancer
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