Cancer cells are quick-change artists adapting to their environment

Until now, researchers have assumed that the growth of solid tumors originates from cancer stem cells characterized by specific surface markers, which develop in a fixed, hierarchical order. Accordingly, such cancer stem cells are responsible for tumor progression and produce specific types of more differentiated cancer cells whose fates are predetermined. In a joint interdisciplinary project led by the Luxembourg Institute of Health (LIH), researchers now show that cancer cells of glioblastomas - conspicuously aggressive solid brain tumors - manifest developmental plasticity and their phenotypic characteristics are less constrained than believed. Cancer stem cells, including their progeny, are able to adapt to environmental conditions and undergo reversible transformations into various cell types, thereby altering their surface structures. The results imply that novel therapeutic approaches, which target specific surface structures of cancer stem cells, will be of limited utility. The research team has published its findings in Nature Communications in April 2019.

Glioblastomas are the most common malignant brain tumors. Because of their rapid growth, the prognosis for those affected is usually dismal. Many patients hold out hopes for novel therapeutic approaches, which utilize drug-bound antibodies directed against specific markers present on the surface of a subpopulation of immature glioblastoma cells. These antibody-drug conjugates bind to the surface, are then internalized and kill the cancer stem cells.

Remarkable cell state transitions

However, results now published in the journal Nature Communications suggest that this approach may be misdirected: 'We exposed cancer cells in the laboratory to certain stressors, such as drug treatment or oxygen deficiency', explains Dr. Anna Golebiewska, Junior Principal Investigator at the NORLUX Neuro-Oncology Laboratory in LIH's Department of Oncology and co-first author of the study. 'We were able to show that glioblastoma cells react flexibly to such stress factors and simply transform themselves at any time into cell types with a different set of surface markers.' This plasticity allows the cells to adapt to their microenvironment and reach a favorable environment-specific heterogeneity that enables them to sustain and grow, and mostly likely to escape also therapeutic attacks.

The team of scientists from Luxembourg, Norway and Germany, led by Prof. Simone P. Niclou at LIH, proposes that neoplastic cells of other tumor types may be also less constrained by defined hierarchical principles, but rather can adapt their characteristics to the prevailing environmental conditions. 'The same phenomenon has been observed in breast and skin cancer', says Dr. Golebiewska. 'This observation predicts that cancer therapies specifically directed against cancer stem cell markers may not be successful in patients.'

The new findings could help to optimize future standard treatments. In laboratory experiments, the researchers were able to show that environmental factors, such as lack of oxygen in combination with signals from the tumor microenvironment can induce cancer cells to modify their characteristics. This microenvironment, the immediate surrounding of the cancer, comprises cells and molecules that influence the growth of the tumor. 'Once we understand exactly what causes the plasticity of tumor cells, we can devise combination therapies which target the signals underlying plasticity and thereby improve the therapeutic impact', underlines Dr. Golebiewska.

Collaboration and funding

The study is a collaborative work between the NORLUX Neuro-Oncology Laboratory and other research units and platforms at LIH. The researchers from LIH also worked in close collaboration with their long-term national partners to whom they are tightly connected through transversal research programmes: the Luxembourg Centre for Systems Biomedicine at the University of Luxembourg and the Department of Neurosurgery of the Centre Hospitalier de Luxembourg. Moreover, the project was carried out with international partners from the Technische Universität Dresden, Germany, the University of Heidelberg, Germany, and the University of Bergen, Norway. This joint undertaking of different research and clinical players gives a truly interdisciplinary dimension to the study.

Anne Dirkse, Anna Golebiewska, Thomas Buder, Petr V Nazarov, Arnaud Muller, Suresh Poovathingal, Nicolaas H. C. Brons, Sonia Leite, Nicolas Sauvageot, Dzjemma Sarkisjan, Mathieu Seyfrid, Sabrina Fritah, Daniel Stieber, Alessandro Michelucci, Frank Hertel, Christel Herold-Mende, Francisco Azuaje, Alexander Skupin, Rolf Bjerkvig, Andreas Deutsch, Anja Voss-Böhme, Simone P Niclou.
Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment.
Nature Communications 10, Article number: 1787 (2019). doi: 10.1038/s41467-019-09853-z.

Most Popular Now

Amgen and Allergan's MVASI™ (bevacizumab-awwb) and…

Amgen (NASDAQ:AMGN) and Allergan plc (NYSE:AGN) announced that MVASI™ (bevacizumab-awwb), a biosimilar to Avastin® (bevacizumab), and KANJINTITM (trastuzumab-anns), a bio...

Compound found in red wine opens door for new trea…

Like to unwind with a glass of red wine after a stressful day? Don't give alcohol all the credit. New research has revealed that the plant compound resveratrol, which is ...

Mylan and Upjohn, a division of Pfizer, to combine…

HERTFORDSHIRE, England & PITTSBURGH & Mylan N.V. (Nasdaq: MYL) and Pfizer Inc. (NYSE: PFE) today announced a definitive agreement to combine Mylan with Upjohn, Pfizer's o...

HIV vaccine nears clinical trial following new fin…

A promising vaccine that clears an HIV-like virus from monkeys is closer to human testing after a new, weakened version of the vaccine has been shown to provide similar p...

Closing the door: breaking new ground related to a…

In order to sustain fast growth, cancer cells need to take up nutrients at a faster rate than healthy cells. The human glutamine transporter ASCT2 allows the amino acid g...

Leading oncologists and nutritionists pinpoint are…

An international collaborative led by Ludwig Cancer Research and Cancer Research UK has identified key areas that are central to uncovering the complex relationship betwe...

Roche and Spark Therapeutics, Inc. announce extens…

Roche (SIX: RO, ROG; OTCQX: RHHBY) and Spark Therapeutics, Inc. (NASDAQ: ONCE) ("Spark") announced that Roche has extended the offering period of its previously announced...

Rye is healthy, thanks to an interplay of microbes

Eating rye comes with a variety of health benefits. A new study from the University of Eastern Finland now shows that both lactic acid bacteria and gut bacteria contribut...

Eating more plant-based foods may be linked to bet…

Eating mostly plant-based foods and fewer animal-based foods may be linked to better heart health and a lower risk of dying from a heart attack, stroke or other cardiovas...

FDA approves first treatment for severe hypoglycem…

The U.S. Food and Drug Administration today approved Baqsimi nasal powder, the first glucagon therapy approved for the emergency treatment of severe hypoglycemia that c...

GSK completes transaction with Pfizer to form new …

The Joint Venture brings together two highly complementary portfolios of trusted consumer health brands, including GSK's Sensodyne, Voltaren and Panadol and Pfizer's Advi...

Bayer acquires BlueRock Therapeutics to build lead…

Bayer AG and BlueRock Therapeutics today announced an agreement under which Bayer will fully acquire BlueRock Therapeutics, a privately held US-headquartered biotechnolog...