Senescent cells actually promote glioblastoma progression

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Senescent cells actually promote glioblastoma progression

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Senescent cells actually promote glioblastoma progression.

Glioblastoma is the most common malignant tumor in the adult brain. They resist conventional treatments, including surgery, radiation and chemotherapy. Despite these therapeutic weapons, glioblastoma inevitably recurs.

In a new study, Isabelle Le Roux at the Paris Institute for Brain Research in France and her team found that eliminating senescent cells, cells that have stopped dividing, can alter a tumor’s ecosystem and slow its progression.

These results open up new avenues for treating this cancer.

The relevant research results were published in the journal Nature Communications on January 17, 2023. The title of the paper is “Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma”.

Glioblastoma is the most common adult brain cancer, affecting 2 to 5 in 100,000 people.

Although the incidence of the disease is highest among people between the ages of 55 and 85, it is increasing in all age groups.

This effect cannot be attributed solely to improvements in diagnostic techniques, suggesting the influence of so far unidentified environmental factors.

People with the disease have a median survival of 15 months after diagnosis because the tumors quickly infiltrate the brain. Le Roux explained, “There is an urgent need to better understand the biology of this tumor, including the diversity of cell types it is composed of and their roles. Our challenge is to find new therapeutic targets and substantially increase the lifespan of patients.” .”

Finding a weak spot in glioblastoma is not an easy task. A recent approach involves targeting a key biological process: cellular senescence. It was originally discovered during the normal aging process of cells, corresponding to the loss of the cell’s ability to divide. The disruption of the cell cycle has a benefit: It prevents the uncontrolled division of malignant cells. In this case, aging contributes to the body’s anti-tumor response.

Alexa Saliou, co-first author of the paper, said, “Cellular senescence has long been considered a simple hallmark of aging, and we now know that it occurs throughout life, especially in response to genotoxic stress, a type of Events that damage DNA, such as chemotherapy.”

When cells enter senescence, they secrete a variety of molecules. This is known as the aging-associated secretory phenotype, or secretome. Saliou added, “The secretome can affect the cellular environment in beneficial or harmful ways. For example, it can activate the immune system or, conversely, induce the formation of blood vessels that help water cancerous tissue. It all depends on what is secreted.” molecular.”

While the effects of cellular aging may seem paradoxical at first glance, recent research has shown that it’s all about timing…and context.

Le Roux explained, “In the short term, the secretome is involved in recruiting immune cells to destroy tumor cells.

But in the long term, the accumulation of senescent cells can promote the destruction of the extracellular matrix — which allows cells to form tissues as well as malignant tumor cells. proliferation.”

The authors wondered whether cellular senescence was present in glioblastoma and, if so, what role it might play in cancer progression. To do this, they studied animal models of glioblastoma and tumor tissue removed from patients during surgery.

Identification of senescent cells in patient and mouse gliomas. Image via Nature Communications, 2023, doi:10.1038/s41467-023-36124-9.

They first looked at tumors from 28 glioblastoma patients. They found that different proportions (0.4 percent to 7 percent of the original mass of glioblastoma) of senescent cells of different cell types — tumor cells, immune immune or glial cells — were predominantly located in areas of malignant cell proliferation and Necrotic area.

In mice, suppressing a subset of senescent tumor cells made it possible to alter immune activity within tumors and extend their lifespan.

The authors then identified a signature genetic signature of cellular senescence based on the expression of 31 genes in mice and ensured that it was the same in humans.

Saliou added, “We observed that strong expression of this gene signature was associated with poor prognosis. This shows a tumor-promoting role of cellular senescence in glioblastoma.”

Therefore, modulating cellular senescence may become a new therapeutic avenue that, when combined with conventional treatments, enhances their effectiveness.

“Eventually, we might consider treating patients with senolytics, molecules that target senescent cells to destroy them,” Saliou said. The emergence of novel senolytics of the blood-brain barrier. This is a major current challenge, because few therapeutic molecules are able to enter the brain. If they are to be incorporated into the treatment of patients, they also need to cause few side effects. There are still many Long way to go.”

References:

Rana Salam et a. Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma. Nature Communications, 2023, doi:10.1038/s41467-023-36124-9.

Senescent cells actually promote glioblastoma progression

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