Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breast cancer progression – The devil is in the detail

27.04.2016

Researchers at Helmholtz Zentrum München describe how breast cancer cells challenged with a small-molecule inhibitor targeting specific invasive properties switch to an alternative mode-of-action, rendering them even more aggressive. The results may impair future therapeutic approaches in the TGF-beta pathway and are published in the journal ‘Oncotarget’.

As breast cancer develops, tumor cells begin to breach the tissue compartment that normally confines the mammary gland and actively invade and spread into the surrounding tissue.


Detail of breast cancer cells in 3D-culture, collectively invading into the surrounding extracellular matrix.

Source: Diana Dragoi / Helmholtz Zentrum München

The research team, led by Dr. Christina Scheel attempted to block this process by exposing cancer cells to a small-molecule inhibitor targeting the TGF-beta Receptor Type I (TGFBR1). TGFBR1 is a crucial relay-protein in a signaling cascade known to endow breast cancer cells with the ability to invade.

Indeed, by doing so the scientist of the Institute of stem cell research were able to prevent a master regulator of genes involved in this process from initiating a cellular program that results in invasive behaviour of cancer cells.

This master regulator, Twist1, has long been implicated in breast cancer progression, but constitutes a type of protein that is currently not amenable to therapeutic targeting. Therefore, the researchers aimed to inhibit other, targetable signaling pathways that Twist1 depends on in order to mediate invasiveness.

Surprising results reveal the adaptiveness of breast cancer cells

“Initially, using conventional in vitro tissue culture techniques, our results indicated that we were indeed successful, as many of the previously described effects of Twist1-activation were prevented by simultaneously blocking TGFBR1” says Diana Dragoi, PhD student at ISF and first author on the study. However, when the researchers transferred the breast cancer cells to a more physiological, 3D-environment, they discovered to their great surprise that Twist1 was able to render breast cancer cells invasive even while TGFBR1 signaling was blocked.

The breast cancer cells had simply switched to an alternative mode of invasion, spreading through the 3D-environment as cohesive strands of cells, instead of single cells. Moreover, these cells had significantly higher rates of proliferation, suggesting they were better equipped to launch secondary tumors after disseminating to distant sites. This latter process, termed metastasis, is the major course of morbidity for breast cancer patients: systemic dissemination and subsequent growth of breast cancer cells in vital organs such as the brain, bone marrow or liver eventually leads to their destruction.

“Taken together, our study suggests that the inhibition of TGFBR1 does not simply block the ability of master regulator Twist1 to induce invasiveness in breast cancer cells, but redirects the actions of Twist1 to generate breast cancer cells that may be even more aggressive” adds co-author Anja Krattenmacher (ISF). “These data highlight the importance of diligent preclinical tests that aim to approximate in vivo conditions as much as possible and to test many different parameters. This is especially important when aiming to interfere with such a complex, multi-step process as metastasis” concludes Dr. Scheel. In the complexity of breast cancer progression, the devil is in the detail.

Further Information

Background
About 70.000 Women are diagnosed with breast cancer every year in Germany alone. Despite significant progress in treatment, rapid adaptation in some aggressive subtypes of breast cancer causes therapeutic resistance and relapse. Therefore, elucidating how breast cancer cells adapt to therapeutic intervention is crucial for the development of effective treatment strategies.

Original Publication:
Dragoi D. et al. (2016). Twist1 induces distinct cell states depending on TGFBR1-activation, Oncotarget, DOI: 10.18632/oncotarget.8878 http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=a...

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. https://www.helmholtz-muenchen.de/en/index.html

The Institute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue.https://www.helmholtz-muenchen.de/en/isf/index.html

Media Contact
Department of Communication, Helmholtz Center Munich – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel: +49-89-3187-2238 - Fax: 089-3187-3324 - E-Mail: presse@helmholtz-muenchen.de

Scientific Contact at Helmholtz Zentrum München
Dr. Christina Scheel, Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Stem Cell Research, Independent Junior Group Mammary Stem Cells. Ingolstädter Landstr. 1, 85764 Neuherberg, Germany - Tel +49-89-3187-2012 - E-Mail: christina.scheel@helmholtz-muenchen.de

Weitere Informationen:

https://www.helmholtz-muenchen.de/en/news/latest-news/press-information-news/art... - link to the press release

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>