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Understanding what drives cancer


How do cancer cells communicate?

While science has come a long way, many questions remain on the journey to preventing and curing cancer. There are 100-200 types of cancer. Cancer types are usually named after the organs or tissues in which they originate. Leukaemia is a group of blood cancers that begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called blasts or leukaemia cells.

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This image was made by cancer researchers in Luxembourg who are investigating leukaemia, a group of blood cancers. Here we see three overlapping cells (recognisable by the nuclei in blue) with their cytoskeleton (in red) absorbing small particles (green) – known as exosomes – released by leukaemia cells.
This video and the image above were captured with the help of PhD researcher Ernesto Gargiulo (CANBIO DTU), together with Dr. Celine Hoffman, who is in charge of the imaging facility at the Luxembourg Institute of Health (LIH).

Exosomes are nanovesicles (30 to 150 nm in diameter), much smaller than cells, produced by all cells in the body. Cells use them to send messages in the form of biological material. The cell receiving the message will modify its behaviour depending on the information contained in the exosome.

The cytoskeleton is a kind of scaffolding present in all cells. It is made of proteins such as actin. It helps cells keep their shape, protects them and enables them to move, with the help of specific flexible structures. It facilitates transport inside the cell, in a compartment called cytoplasm, by enabling the movement of vesicles and organelles, and plays a role in cell division.

What role does this play in cancer research? Leukaemia cell exosomes promote cancer progression

Tumour cells make use of exosomes to communicate with surrounding cells. Which impact this has depends on the type of cancer and the receiving cells.

Researchers Dr. Jerome Paggetti and Dr. Etienne Moussay from the Luxembourg Institute of Health (LIH) lead the Tumor-Stroma Interactions Group (TSI), which investigates the role this communication plays in leukaemia.

Reprogramming the environment

The scientists have discovered that the messages – exosomes – sent by leukaemia cells play a key role in the progression of the disease: they reprogram the environment around the tumour in such a way that it helps the survival of the cancer cells, prevents the immune system from acting, and therefore contributes to the spread of the cancer.

This research is supported jointly by the FNR and Fondation Cancer.

Shedding light on the most aggressive brain tumour

LIH cancer researchers Prof Simone Niclou and Dr Anna Golebiewska lead a team of researchers studying brain tumours.

Much of the NORLUX Neuro-Oncology lab’s work is focussed on Glioblastomas, the most aggressive brain tumour – it has finger-like tentacles that infiltrate the brain, making them very difficult to remove completely.

95% mortality rate

Because of their rapid growth, the prognosis for patients is usually bleak: With standard treatment (surgery, radiation and chemotherapy), survival 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 artists George Gershwin and François Truffaut, as well as US Senator John McCain and Beau Biden, son of US President Joe Biden.

Discovery: Glioblastoma cells adapt to their environment

Having worked on dozens of research projects, the team has for example discovered that Glioblastoma cells quickly adapt to their environment and transform their surface structure, insights that could help optimise future treatments.

The team was recognised with a 2021 FNR Award in the category Outstanding Scientific Achievement for their research advances in glioblastoma research.

In a different project, funded jointly by the FNR and Fondation Cancer, the team wants to characterise the molecular and genetic differences between primary and recurrent brain tumours, before testing their responses to different new and existing drugs. The ultimate goal is to have personalised treatment options for recurrent glioma patients, for whom the standard care has not been successful.

3D brain tumour organoids during drug treatment (dead cells = red; green = viable cells). The researchers use these organoids to better understand what happens during treatment.
Glioblastoma cells growing in different microenvironments
Discover more about this research project in our video:

Actin(g) as protection: a barrier stopping cancer cells from getting attacked?

Our body is incredible: our immune system has killer cells patrolling and attacking unhealthy cells, such as cancer cells. However, sometimes cancer cells can avoid being attacked, leading to immune evasion and disease progression. Science wants to understand the different factors responsible for this in order to elaborate new therapeutic strategies aimed at restoring or improving immune cell ability to destroy cancer cells.

The Cytoskeleton and Cancer Progression group, led by Dr Clément Thomas, has discovered that the actin cytoskeleton plays a critical role in cancer cell immune evasion. The scientists showed that as immune cells, such as Natural Killer cells, go to attack cancer cells, a massive accumulation of a protein called actin can happen at the interface between the two types of cells. The team suspects that the so-called “actin response” acts as a physical barrier, preventing the NK cell from destroying the cancer cell. The researchers are working on a project to better understand this process, focusing particularly on breast cancer, the leading cause of cancer death in women in Luxembourg.

Read a feature about one of this Group’s discoveries or an abstract of one of their other FNR-supported research projects.

Microscopy picture of a breast cancer cell mass or “spheroid” (in green) attacked by immune cells (in orange). Cell nuclei appear in blue. Some cancer cells are able to mount an actin barrier at the cell-to-cell interface (bright green areas), which protects them against immune cells. Picture by Dr Celine Hoffmann, researcher in the Cytoskeleton and Cancer Progression group, LIH.

Studying the microenvironment of colon cancer

Colorectal cancer (CRC) is one of the most frequent and deadly cancers in the world with 1.2 million diagnoses and around 600,000 deaths each year. In Luxembourg, CRC is one of the deadliest cancers, both among men and women. As with other cancers, early diagnosis and treatment increases the chances of survival.

Scientists have found evidence bacteria in the gut are an important factor in CRC, but are they a cause or a consequence? Researchers from the Molecular Disease Mechanisms group at the University of Luxembourg study the microenvironment of colon cancer, with the goal of answering this question and finding new treatments.

Organoids derived from a human CRC tissue specimen from the team’s national CRC cohort. Organoids are tiny, self-organised three-dimensional tissue cultures that are derived from stem cells. Such cultures can be crafted to replicate much of the complexity of an organ, or to express selected aspects of it. Letellier and team use them for performing in vitro experiments in the lab.

Lifestyle and food choices have been shown to influence the bacteria in our gut. In a new project, Dr Elisabeth Letellier and her team are investigating whether changes in bacteria could be responsible for kickstarting the growth of a tumour. If the answer is yes, the goal is to pinpoint which bacteria or bacterial community exactly take part in this process. The team will also test if different diets have any impact on cancer progression, possibly helping in the development of dietary guidelines for CRC patients.

Elisabeth Letellier’s research is supported jointly by the FNR and Fondation Cancer.

CANBIO: Training the next generation of cancer researchers

Science has come a long way in understanding cancer, but much more research is needed before this disease can be beaten. Training the next generation of scientists is essential.

The Cancer Biology (CANBIO) Doctoral Training Unit (DTU) aims to do just this, by bringing together 12 Luxembourg-based research teams with different specialties to train 18 young scientists in cancer biology. Working together, the PhD students study tumours on a molecular level, look for biomarkers, investigate why some tumours become resistant to treatment, research new ways to treat cancer, and build computational disease models to facilitate innovative translational research. The common thread in these approaches: All the projects gravitate around the goal of understanding why tumours progress, and why they return. The training programme involves Luxembourg Institute of Health, the University of Luxembourg and the Laboratoire National de Santé, in collaboration with national and international partners, including the Centre Hospitalier de Luxembourg (CHL), the University of Bergen (Norway) and the University of Paris-Saclay (France). All of the research groups featured on this page are involved in the programme. The FNR funds the majority of the PhD candidates in the programme through the dedicated PRIDE programme.