Brain cancer: Cancer cells can change and adapt to their environment

 

An international, interdisciplinary team of scientists, led by the Luxembourg of Health (LIH), has been able to show that the cells of Glioblastoma – an extremely aggressive type of brain tumour – can adapt to their environment and transform their surface structure. The new insights could help optimise future treatments.

Glioblastomas are the most common malignant brain tumors. Glioblastomas have finger-like tentacles that infiltrate the brain, which makes them very difficult to remove completely. Because of their rapid growth, the prognosis for patients is usually dismal: With standard treatment, (surgery, radiation and chemotherapy) survival after diagnosis is only 12 – 15 months on average, with less than 5% of patients surviving longer than five years. Notable people who have died of Glioblastoma include US Senator John McCain and Ted Kennedy, son of John F. Kennedy.

Many patients hold out hope for novel therapeutic approaches, which utilise 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 internalised and kill the cancer stem cells.

Implications for therapies involving targeting of cancer stem cells

Until now, scientists have assumed that the growth of solid tumours (tumours that do not contain any liquid or cysts) originates from cancer stem cells, characterised by specific surface markers, which develop in a fixed, hierarchical order. Such cancer stem cells play a key role in the tumour progression, and they produce specific types of more differentiated cancer cells whose fates are predetermined.

However, a joint interdisciplinary project led by the Luxembourg Institute of Health (LIH), researchers have shown that cancer cells of glioblastomas manifest developmental plasticity – the ability to change their physiological characteristics. The scientists also found that the phenotypic characteristics of glioblastoma cells are less constrained than believed.

Cancer stem cells, including their ‘offspring’, can 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.

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 also to escape therapeutic attacks.

Same phenomenon observed in breast and skin cancer

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.”

Using new insights to improve treatment

The new findings could help optimise 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.

The study is a major part of the AFR PhD thesis of Dr Anne Dirkse, co-first author on the publication, who was supported by an AFR PhD grant and a training grant from the Fondation du Pélican de Mie et Pierre Hippert-Faber (Fondation de Luxembourg). Furthermore, the work was supported by funding from LIH, Sächsisches Staatsministerium für Wissenschaft und Kunst (SMWK), Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft (DFG).

Publication

The research team published its findings (open access) in Nature Communications in April 2019. (Dirkse, Golebiewska et al. Nature Communications 2019, DOI: 10.1038/s41467-019-09853-z).

A glioblastoma seen on an MRI scan. (source: CC BY 2.5). The prevalence of Glioblastoma is 2-3 in 100.000 people (Canada, United States, Europe).

RELATED PROGRAMMES

More from the domains Life Sciences, Biology & Medicine

Opinion: Fake News about the Corona Virus and science in general

Luxembourg Parkinson’s Study: 1600 participants recruited!

FNR 20 years: An evening with science [fiction] in the House of Frankenstein

Toward a better understanding and diagnosis of neurodegeneration and brain tumours

From lab to spin-off: NIUM – nutrition as a therapeutic tool

Microbiome research: unlocking basic unknowns in human health

Spotlight on Young Researchers: Remko Nijzink

A modern and high quality environment for doctoral candidates in Luxembourg

The immune system: A delicate balance

Science meets rock’n’roll: what happens when a palaeontologist has a penchant for extreme metal music

10 years of Mr Science

Spotlight on Young Researchers: Understanding our immune system

Spotlight on Young Researchers: Carole Lara Veiga de Sousa

Diet and bacteria combination limits cancer progression

Spotlight on Young Researchers: Sebastian Scheer

Sharing insights to inspire the next generation

Spotlight on Young Researchers: Ernesto Gargiulo

Connecting fundamental research and clinical care

Triggered by fever: Enzyme mutation plays key role in novel fatal neurological disorder in children

Study reveals caesarean birth impacts child’s immune system

FNR ATTRACT Fellows – the people behind the science: Stan Schymanski

Shedding light on how colon cancer develops and progresses

From flood prediction to deep brain stimulation

“It was truly inspiring how new and older generations of scientists share ideas”

FNR ATTRACT Fellows – the people behind the science: Anne Grünewald

Spotlight on Young Researchers: Gilles Tossing

Luxembourg researchers discover significant lab kit contamination; team up with company to find solution

Spotlight on Young Researchers: Anna Monzel

AFR Postdoc: Biology of Ageing – A small protein with big potential

ATTRACT: Human metabolism as a computer model

Spotlight on Young Researchers: Antoun Al Absi

Spotlight on Young Researchers: Katharina Baum

FNR ATTRACT Fellows – the people behind the science: Paul Wilmes

Spotlight on Young Researchers: Amy Parrish

Spotlight on Young Researchers: Maria Pires Pacheco

FNR ATTRACT Fellows – the people behind the science: Ines Thiele

Research trends: Remote control from within – gut bacteria have an influence on neurological diseases

FNR ATTRACT Fellows – the people behind the science: Dirk Brenner

INTER: Luxembourg researcher in bilateral epigenetics project

Does Parkinson’s disease originate outside the brain? FNR ATTRACT Fellow leads study suggesting gut bacteria could play a role

Spotlight on Young Researchers: Xianqing Mao

Spotlight on Young Researchers: Lisa Hefele

ATTRACT: The female perspective

Spotlight on Young Researchers: Charles de Bourcy

Spotlight on Young Researchers: Kacy Greenhalgh

Spotlight on Young Researchers: Léon-Charles Tranchevent

Twisted: CORE project leads to innovative interdisciplinary conference

POC: Pocket-sized intestines – the HuMiX model enables intestinal flora to be investigated under real conditions

INTER Mobility: Lack of fibre makes intestinal bacteria aggressive

Spotlight on Young Researchers: Multiple nationalities, one goal

Spotlight on Young Researchers: Jo Hoeser

FNR ATTRACT Fellow in significant immunology discovery

Spotlight on Young Researchers: Pit Ullmann

Spotlight on Young Researchers: Nina Hentzen

Women in Science: Simone Niclou, oncologist

CORE Spotlight: How do eating disorders develop?

Luxembourg researchers develop computer models for hundreds of bacterial strains

Researchers’ Days: What it feels like to have Parkinson’s disease

Spotlight on Young Researchers: Cyrille Thinnes

How do malaria pathogens spread? Interview with biologist Philip Birget

NCER-PD: Meet Dany, the 100th Parkinson’s study control person

A Centre of Excellence in Research on Parkinson’s disease (NCER-PD)

Meeting with 65 Nobel Prize Winners in Lindau: Interview with Charles de Bourcy

RESCOM Spotlight: Largest medical congress in Luxembourg’s history

ATTRACT SPOTLIGHT: Exploring microbial ecosystems in humans

Interview with Gökhan Ertaylan: “Nobel Prize Winners are also just people”

This site uses cookies. By continuing to use this site, you agree to the use of cookies for analytics purposes. Find out more in our Privacy Statement