Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover a possible reason for drug resistance in breast tumors

20.07.2015

HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth. However, two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood. Researchers now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.

For their studies researchers from the INM – Leibniz-Institute for New Materials, Saarbrücken and from the German Cancer Research Center (DKFZ) in Heidelberg used a new electron microscopy method called Liquid STEM. It allows nanoscale studies of intact cells in their native liquid environment.

The scientists have studied the local variations of HER2 membrane protein and of its dimers. HER2 is a member of the human epidermal growth factor receptor (EGFR) family. These family members trigger cell growth signals, when two of the membrane proteins are bound into a protein complex (dimerization).

This happens usually after the binding of a small protein, the epidermal growth factor, which circulates in the blood stream and serves as communicator to transmit signals that regulate cell growth. HER2 is special in the sense that it does not need the growth factor protein in order to form dimers. It is thus capable of triggering cell growth without external regulation.

In certain types of breast cancer, amplified levels of HER2 and its dimerization are known to drive unrestricted cell growth. HER2-tailored antibody-based therapeutics entered clinical practice more than a decade ago. These drugs aim to prevent cell growth triggered by HER2 homo- and/or heterodimerization.

“We found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 cells. Could such cells survive the therapy and then develop into a drug resistant cancer at a later stage? It thus seems to be of key significance to study this sub-population of cells with exceptional phenotype,” says Niels de Jonge, head of the Innovative Electron Microscopy group.

HER2 dimerization processes were thus far mostly studied on the basis of cell population averages, for example, with biochemical methods using pooled cell material, and information about the localization of HER2 dimerization was lacking. Therefore, the researchers around de Jonge pioneered the electron microscopy method Liquid STEM to imaging these receptors on cancer cells. The cells were examined on a microchip placed in the electron microscope, and remained intact and in liquid.

“Specimens cannot be studied in liquid with traditional electron microscopy”, explains Professor de Jonge. “Cells are typically studied in dry state via thin sectioning of solid dried plastic embedded or frozen material. The role of HER proteins is a "hot" topic in cancer research but despite large research efforts using a wide range of techniques over the past decades this important information was not unveiled before. Our novel findings were obtained as a direct consequence of the high spatial resolution of Liquid STEM combined with its capability to study many intact cells in liquid,” says de Jonge.

Original Publication:
“Local variations of HER2 dimerization in breast cancer cells discovered by correlative fluorescence and liquid electron microscopy” was published in the new online journal Science Advances Sci. Adv. 1, e1500165 (2015) by D. B. Peckys, U. Korf, N. de Jonge.

The research was conducted by Prof. Dr. Niels de Jonge, Dr. Diana B. Peckys of the INM – Leibniz-Institute for New Materials in Saarbrücken together with the group of Dr. Ulrike Korf, Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ) in Heidelberg, Germany.

Your expert:
Prof. Niels de Jonge
INM – Leibniz Institute for New Materials
Head Innovative Electron Microscopy
Phone: +49681-9300-313
niels.dejonge(at)leibniz-inm.de

INM conducts research and development to create new materials – for today, tomorrow and beyond. Chemists, physicists, biologists, materials scientists and engineers team up to focus on these essential questions: Which material properties are new, how can they be investigated and how can they be tailored for industrial applications in the future? Four research thrusts determine the current developments at INM: New materials for energy application, new concepts for medical surfaces, new surface materials for tribological systems and nano safety and nano bio. Research at INM is performed in three fields: Nanocomposite Technology, Interface Materials, and Bio Interfaces.
INM – Leibniz Institute for New Materials, situated in Saarbrücken, is an internationally leading centre for materials research. It is an institute of the Leibniz Association and has about 210 employees.

Weitere Informationen:

http://www.leibniz-inm.de/en
http://www.leibniz-gemeinschaft.de

Dr. Carola Jung | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>