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Reprogramming cancer cells to impair glioblastoma growth

Image of the control and treated graft
Control (right) and treated (left). Image credit: Francesco Trovato.

Lund Stem Cell Center researchers from Lund University and Skåne University Hospital have uncovered a way to impair the growth and progression of glioblastoma tumor cells - the most aggressive form of brain cancer. The study, published in Molecular Cancer Therapeutics, shows it is possible to transform these cancer cells into cells that resemble normal, mature astrocytes.

Nearly half of all cancerous brain tumors are glioblastomas, an aggressive type of cancer. This type of tumor grows rapidly and can spread throughout the brain making it difficult to treat - with about 40% of patients surviving the first-year post-diagnosis. Treatments, which typically include surgery followed by radiation and chemotherapy, mainly work to prolong, and improve a patient’s quality of life by easing symptoms and slowing cancer growth.

To improve treatment options and outcomes for patients, a team of researchers at Lund Stem Cell Center, based at Lund University and Skåne University Hospital in Lund, are exploring whether a potential treatment can be developed by reprogramming cancer cells into cells that, as far as possible, function normally.

“We had the idea to use a reprogramming approach on these aggressive, malignant brain tumor cells. Reprogramming is a technique that can activate certain genes that can redirect one cell type into another. Here, we wanted to push the cancer cells towards something less harsh, less aggressive,” explained Johan Bengzon, Professor of Neurosurgery. 

Reprogramming glioblastoma tumor cells into astrocytes

Glioblastomas are thought to arise from the cancerous transformation of glial cells, the brain’s support cells. Current research indicates that astrocytes - star-shaped glial cells that actively participate in brain signaling and are necessary for the healthy function of neurons and the brain as a whole - are often co-opted to contribute to glioblastoma progression, meaning they can become cancerous and support tumor growth.

“By taking advantage of the similarities between neural developmental processes and cancer formation, we can attempt to correct the tumor and possibly eliminate the malignant nature of the tumor cells,” stated Francesco Trovato, Postdoctoral Reseacher.

In a proof-of-concept study now published in Molecular Cancer Therapeutics, Francesco Trovato, a postdoctoral researcher in the labs of Henrik Ahlenius and Johan Bengzon, reprogrammed human glioblastoma cells and glioblastoma stem cells, triggering them to develop into mature, astrocyte-like cells.

“The reprogrammed cells acquired astrocyte-like structures and functions. The cells expressed typical glial characteristics, showed a marked decrease in their ability to multiply, and most importantly, exhibited a reduced ability to produce tumors,” described Henrik Ahlenius, Researcher and Principal Investigator.

The results of this new study build on earlier work from the Ahlenius laboratory, which in 2018 presented a method to generate astrocytes from human pluripotent stem cells and, earlier this year, described the efficient reprogramming of human fibroblasts, or skin cells, into astrocytes.

“We hope this method of turning cancer cells into mature, astrocyte-like cells will pave the way for new therapeutic approaches to be added to the treatment toolbox for glioblastoma,” noted Henrik Ahlenius.

Advancing the treatment toolbox for glioblastoma

Based on the findings from this study, the research team has received additional funding to bring their discoveries into the clinic as a potential new gene therapy for patients with glioblastoma and possibly other types of brain tumors. 

With funding from the Erling Persson Foundation (4 million SEK) and Barncancerfonden (1 million SEK), Henrik Ahlenius and Johan Bengzon plan to advance their research to the next stage. They will do this by replicating their method in a pure in vivo setting and reprogramming the tumor cells inside the brains of their animal models. The reprogramming method will also be developed further using human tumor tissue removed during glioblastoma surgery.

“Using human glioblastoma tissue collected during surgery, we will repeat this process using organoids and slice cultures as glioblastoma tissue models. This is the most accurate representation of the processes occurring in human patients that we can recreate in the lab,” revealed Johan Bengzon.

Postdoctoral researcher Francesco Trovato will also continue to explore the use of reprogramming both to dampen glioblastoma tumor expansion and progression and as a model for childhood and adult tumors, thanks to a 3 million SEK postdoctoral fellowship grant he received earlier this spring from the Swedish Society for Medical Research.

“Over the next three years, we intend to implement techniques that are not only possible in a lab setting but can also be applied clinically. We plan to combine reprogramming with genetic engineering to generate specific, genetically tailored models of adult and childhood brain tumors which can be used to evaluate therapies or as a model system to answer certain basic biological questions,” concluded Francesco Trovato.

About the new grant awards:

The Erling Persson Foundation: In 1999, the Erling-Persson Foundation was established, in the founder of the global H&M group's memory. Nearly half of the funding distributed by the Foundation (SEK1.86 million) has gone to research projects at Swedish universities and colleges. Within science, substantial support has been awarded to research in, for example, diabetes, cancer, cardiovascular disease, antibiotic resistance and neurological disease. (4 million SEK)

Barncancerfonden: As the single largest financier of childhood cancer research in Sweden, the Swedish Childhood Cancer Foundation has long served as a hub in the fight against childhood cancer. Barncancerfonden plays a central role in fighting the disease and have been funded almost exclusively by the support of private donors and companies, both large and small. (1 million SEK was awarded for the development of direct cellular reprogramming in pediatric brain tumor treatment and 1.5 million SEK for modeling of early tumorigenic changes in childhood brain cancer.)

The Swedish Society for Medical Research (SSMF): SSMF is a non-profit association that has worked to provide support for medical research in Sweden, since 1919. SSMF’s postdoctoral grants are for postdoctoral research in medical science over a three-year period, with the aim to give young researchers the opportunity to obtain qualifications to establish themselves as independent researchers. (3 million SEK)


Photo of Francesco Trovato.

Francesco Trovato

Postdoctoral Researcher
Stem Cells, Aging, and Neurodegeneration Research Group
Email: Francesco [dot] Trovato [at] med [dot] lu [dot] se

Profile in Lund University research portal

Portrait of Henrik Ahlenius

Henrik Ahlenius

Principal Investigator
Division of Neurology
Department of Clinical Sciences
BMC B10, Lund University
221 84 Lund, Sweden

Phone: + 46 46 222 42 59
Email: Henrik [dot] Ahlenius [at] med [dot] lu [dot] se

Profile in Lund University research portal

Portrait Johan Bengzon

Johan Bengzon

Principal Investigator
Professor of Neurosurgery
Phone: + 46 70 5549500
Email:Johan [dot] Bengzon [at] med [dot] lu [dot] se

Profile in Lund University research portal


Transcription Factor Forced Astrocytic Differentiation Impairs Human Glioblastoma Growth In Vitro and In Vivo

AACR Molecular Cancer Therapeutics, 12 December 2022,

Quick facts: neuroscience research, glioblastoma reprogramming // basic, translational research // In vitro and in vivo studies // Animal study using mice models // Non-randomised intervention in two or more groups

Project Funding:

Funding for this research was provided by the Elsa Schmitz’ foundation, the Segerfalk foundation, the Swedish Society of Medical Research, the Swedish Cancer Society, Region Skåne, and donations from Viveca Jeppsson, Maj‐Britt and Allan Johansson, as well as from grants from the Swedish state under agreement between the Swedish government and county councils (ALF).