Particles of stress lead to obesity-related pancreatic cancer

Dr Grabocka, researcher at Sidney Kimmel Cancer Center – Jefferson Health, said: “Research on stress particles is exploding right now, but there’s still a lot we don’t know regarding them. What does it do and how does it work? and an assistant professor at Thomas Jefferson University. “This work is the first to show that an overload of stress particles can induce tumor growth in the pancreas. Our experiments in mice also showed a complete reversal of the tumor. growth of cancer in the laboratory.”

Stress granules are a type of abnormal cell compartment. The cell produces these membraneless organelles in response to stress and to protect the cell from stress-induced self-destruction. It is a cellular reflex and defense mechanism found throughout the animal and plant worlds. Even tomato plants produce stress seeds to protect their cells. Researchers still don’t know what these organelles are made of and how exactly they protect cells. However, it is clear that cancers have chosen this defense mechanism to their own advantage. Many cancers produce much higher levels of stress particles than normal cells, to help protect cancer cells from triggering natural chains of self-destruction.

Knowing this, Dr. Grabocka’s team created a mouse cancer model to prevent the formation of stress particles in pancreatic cancer in mice. When they removed the genes that regulate the formation of stress particles, they saw a 50% reduction in pancreatic cancer growth in the mice.


“Now,” says Dr. Grabocka, “we must have the tools to answer the question of obesity.” Obesity affects two-thirds of all adults in the US and 50% globally. It also doubles the risk and mortality for pancreatic cancer and increases the risk of other cancers. About 33% of pancreatic cancer cases are linked to obesity, a number that is expected to increase in the coming decades.

The researchers took two different types of mouse models of obesity – one with a genetic predisposition to overeating and the other fed a high-fat diet – and looked at pancreatic cancer in these mice. Both models had 5 to 8 times higher levels of cancer stress particles than non-obese mice. “This suggests to us that cancer in obese mice may depend on particles that stress their growth. When we eliminate what cancer depends on for survival, we will kill the cancer.”

Dr Grabocka said: “When we suppressed stress granulation formation in these obese mice with pancreatic cancer, the results were actually quite surprising. “We didn’t see cancer grow either 1/14th and 1/20th the amount of growth that we see in obese mice with intact stress granules in the tumours.”

And the most striking difference is their overall survivability. Usually in these pancreatic cancer models, mice die very quickly, within 50-60 days. In obese mice whose tumor stress granules were blocked, 40% were cancer-free after 300 days, with no signs of cancer anywhere in the animals. Dr Grabocka said: “This level of response is extremely rare.

These experiments show that stress particles aren’t just present in cancer cells, they actually promote cancer growth in the first place. “This is the first direct evidence linking stress particles with cancer progression,” said Dr.

More importantly, Dr. Grabocka’s lab also identified drug targets that could block the formation of stress particles in obesity-related pancreatic cancer. The next steps are to test existing small-molecule inhibitors to see if they can be translated for use in humans.

“Cellogenic stress conditions, such as obesity, increase the number of stress particles present in cells, and can lead to the formation of pancreatic and other cancers,” said Dr. other mail. “Because the impact we saw was so great, we thought that targeting stress granule formation could become a good candidate for a novel cancer therapy. Ours paves the way for a human clinical trial.”

Source: Eurekalert

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