Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MDC Researchers Discover Why Basal Breast Cancer Can Be So Aggressive

06.12.2013
Breast cancer is the most common cancer in women. One subtype of breast cancer is particularly aggressive: estrogen receptor (ER)-negative basal breast cancer.

Researchers of the Max Delbrück Center (MDC) in Berlin-Buch have now elucidated the key factors for the aggressiveness of this subtype and at the same time have identified targets for the development of new and more effective treatments.

The study by Dr. Jane Holland, Professor Walter Birchmeier, Dr. Balász Györffy (Charité Berlin, Semmelweis University in Budapest, Hungary) as well as Dr. Klaus Eckert (EPO Experimental Pharmacology and Oncology GmbH) has now been published online in the open access journal Cell Reports*.

In contrast to estrogen-positive breast cancer, basal breast cancer is not controlled by this female sex hormone. This cancer subtype lacks hormone receptors, which is why in contrast to estrogen-positive or progesterone-positive breast cancer a “hormone withdrawal” (anti-hormone therapy) has no effect. Progesterone is also a female sex hormone. In the latter form of breast cancer, doctors can suppress the cancer growth with anti-hormone therapies, since drugs block the receptors for estrogen or progesterone on the surface of the cancer cells. Furthermore, breast cancer with receptors for the growth factor Her2 (abbreviation for human epidermal growth factor receptor 2) can be targeted with an antibody which occupies the receptors for Her2.

These therapies are not possible with the basal breast cancer subtype, according to Professor Birchmeier and Dr. Holland. In most cases (about 70 percent), the subtype neither has receptors for estrogen nor for progesterone nor Her2; it is therefore “triple negative”. “Thus, the only possible treatment for this cancer is chemotherapy,” they said. “However, because it is so difficult to treat, researchers and clinicians are seeking new ways to more specifically combat this fast-growing and aggressive type of cancer.

An infamous “triple combination”
Researchers have known for some time that two signaling pathways can play an important role in the malignant growth of basal breast cancer. One is the Wnt/beta-catenin signaling pathway, which Professor Walter Birchmeier’s laboratory has been studying for many years. This signaling pathway is essential for embryonic development, cell growth (proliferation) and cell maturation or cell specialization (differentiation). In the clinic it has been shown that patients with a high beta-catenin level may have basal breast cancer.

In addition, a growth factor is involved which researchers have named after its discovery site in the liver: hepatocyte growth factor/scatter factor (HGF/SF). It is referred to as scatter factor because it can separate cells from their respective cluster. It is therefore important for cancer research, as Professor Walter Birchmeier and his staff were able to demonstrate repeatedly: HGF/SF binds to its receptor (Met) in the cancer cell membrane, thus stimulating cancer growth.

Main driver identified for basal breast cancer
Dr. Holland has now shown that an infamous “triple-combination”, Wnt/beta-catenin and HGF/SF, plus an additional factor are to blame for the growth of basal breast cancer. In an adult mouse model, in which both signaling pathways are simultaneously mutated and activated, she identified the first two main drivers that induce the cancer cells to proliferate. Also involved is a system of signaling proteins (chemokines) that is activated by the two signaling pathways Wnt/beta-catenin and HGF/SF. Jane Holland, – she is Australian – already conducted research on this chemokine system during her doctoral thesis at the University of Adelaide. Mice in which additionally the gene for the receptor CXCR4 of this chemokine system has been inactivated are immune to this type of cancer. “Such genetic experiments clearly show that the third component is essential,” Professor Birchmeier said.

In vitro and in vivo in mice, the researchers in Berlin-Buch tested the various inhibitors that have already undergone clinical trials against other cancers but have not been approved. They proceeded step by step, until they ultimately used combinations of the various inhibitors at all three points of attack. Thus, they succeeded in dramatically suppressing cancer growth in mice. Dr. Holland and Professor Birchmeier explained: “A triple attack that blocks both the chemokine system and the two signaling pathways Wnt/beta-catenin and HGF/Met is the most effective.” Dr. Holland added: “This is shown by the fact that after their breast cancer treatment, the mice again formed normal, so-called alveolar structures instead of tumor tissue.” The researchers now hope that their findings will be used in further preclinical trials, and if successful, will also be applied in clinical research.

* Combined Wnt/-catenin, Met and CXCL12/CXCR4 Signals Characterize Basal Breast Cancer and Predicts Disease Outcome

Jane D. Holland1*, Balázs Győrffy2,3, Regina Vogel1, Klaus Eckert4, Giovanni Valenti1, Liang Fang1, Philipp Lohneis3, Sefer Elezkurtaj3, Ulrike Ziebold1, and Walter Birchmeier1

1 Department of Cancer Research, Max Delbrück Center for Molecular Medicine (MDC), Robert-Roessle-Str. 10, Berlin, Germany
2 Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences - Semmelweis University, Bókay u. 53-54, Budapest, Hungary
3 Institute for Pathology, Charité Medical University, Charitéplatz 1, Berlin, Germany
4 Experimental Pharmacology & Oncology (EPO), Robert-Roessle-Str. 10, Berlin, Germany

http://dx.doi.org/10.1016/j.celrep.2013.11.001

Contact:
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in the Helmholtz Association
Robert-Rössle-Strasse 10; 13125 Berlin, Germany
Phone: +49 (0) 30 94 06 - 38 96; Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Periodic ventilation keeps more pollen out than tilted-open windows

29.03.2017 | Health and Medicine

Researchers discover dust plays prominent role in nutrients of mountain forest ecoystems

29.03.2017 | Earth Sciences

OLED production facility from a single source

29.03.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>