Article 3 min read

Glioblastoma: exchange between healthy cells and cancer cells enables tumor survival

Published the By Christophe Thomas

Why is one of the most aggressive forms of brain cancer, glioblastoma, able to resist treatment so effectively? Scientists have provided some answers to this question by revealing the role of very thin membrane bridges, known as tunneling nanotubes, connecting the tumor to its environment.
  • #Glioblastoma
  • #Brain cancer
  • #Mitochondria
Transfert mitochondrial via un TNT entre des cellules en culture 2D

Three key takeaways:

  1. 1 Glioblastoma cells exchange mitochondria with healthy brain cells
  2. 2 This is an asymmetrical exchange benefiting the tumor, with the cancer cells shedding their damaged mitochondria and retrieving functional mitochondria
  3. 3 TNT-type connections have been visualized for the first time in mice. Mitochondria have also been observed inside tunneling nanotubes, strongly suggesting that mitochondria are exchanged via these structures

Glioblastoma is a highly aggressive form of brain tumor that is extremely difficult to treat. Around 3,500 new cases are diagnosed in France every year. Relapses are common despite the variety of therapeutic approaches available. Median life expectancy post-diagnosis is 14 months and the 5-year survival rate is just 5 to 7%. But what makes this form of brain cancer so difficult to treat? Tunneling nanotubes (TNTs) may be a piece in the puzzle.

Tunneling nanotubes – vital structures for intercellular communication

For over 20 years, Chiara Zurzolo has been studying tunneling nanotubes, which are like highways facilitating communication between cells. They enable cells to exchange molecules, electrical signals and organelles (small structures performing highly specific functions within each cell) over long distances. Although tunneling nanotubes are difficult to investigate, as they are extremely thin and fragile, Chiara Zurzolo's team at the Institut Pasteur demonstrated TNTs' central role in multiple contexts in recent years. Tunneling nanotubes hijacked by SARS-CoV-2 to help it infect neurons also enable the spread of α-synuclein aggregates, which cause Parkinson's disease. While previous studies were conducted in vitro, the existence of nanotubes was formally demonstrated in animals a few months ago. Even more recently, scientists revealed how mitochondria – the cells' powerhouses – stimulate TNT formation in Parkinson's disease when damaged.

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An exchange enabling cancer cells to resist metabolic stress

This pairing of tunneling nanotubes and mitochondria also plays a key role in glioblastoma. In a recent study, scientists demonstrated that tumor cells exchange mitochondria with astrocytes, a type of brain cell that notably protects neurons. Remarkably, this exchange between healthy cells and cancer cells is asymmetrical, in other words the tumor cells transfer damaged mitochondria to astrocytes (which then degrade them), whereas astrocytes transfer functional mitochondria to cancer cells. This "trade" probably allows the cancer cells' mitochondria to continue functioning normally and adapt to metabolic stress, thus promoting tumor survival and progression.

Tunneling nanotubes and mitochondria: proof in the form of in vivo images

This exchange of mitochondria very likely occurs via – you guessed it – tunneling nanotubes. As previously mentioned, these intercellular highways are extremely thin and fragile, so the successful in vivo visualization of mitochondrial transfer via TNTs was one of the study's key accomplishments. To achieve this, the scientists used the cutting-edge technique of intravital subcellular microscopy. This enabled the team to directly observe TNT-type connections and the presence of mitochondria within them in mice.

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Intercellular mitochondrial transfer via a TNT in 2D culture (with the mitochondria in red and actin, the main constituent of TNTs, in cyan) - Ines Saenz-de-Santa-Maria et Chiara Zurzolo

Although we are still a long way from understanding exactly how glioblastoma cells hijack healthy cells to their own advantage, this study opens up potential new therapeutic avenues. By targeting tunneling nanotubes, it could be possible to disrupt mitochondrial transfer, cancer cell metabolism, and ultimately, tumor survival.

This work on glioblastoma falls under the "Origins of diseases" scientific priority of the Pasteur 2030 strategic plan aimed at investigating the mechanisms underlying non-communicable and inflammatory diseases. 

Source : Tunneling nanotubes regulate mitochondrial homeostasis between glioblastoma and astrocytes, and between tumor cells in vivo, Nature communications, September 15, 2026


Ines Saenz-de-Santa-Maria1,2,3, Anna Pepe1, Jean-Yves Tinevez4, Christel Brou1, Yakov Vitrenko5, Thomas Cokelaer6, Elizabeth Cohen-Jonathan Moyal7, Roberto Weigert8 & Chiara Zurzolo1

1Membrane Traffic and Pathogenesis Unit, Institut Pasteur, Université Paris Cité, CNRSUMR 3691, Paris, France. 
2Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. 
3Polymer Therapeutics Lab, Prince Felipe Research Center (CIPF), Valencia, Spain.
4Institut Pasteur, Université Paris Cité, Image Analysis Hub, Paris, France. 
5Institut Pasteur, Université Paris Cité, Plate-forme Technologique Biomics, Paris, France. 
6Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France. 
7Université de Toulouse, Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM), Oncopole Claudius Regaud, Toulouse, France. 
8National Institutes of Health, Center for Cancer Research, National Cancer Institute, Laboratory of Cellular and Molecular Biology, Bethesda, MD, USA.