Scientists Discover Mechanic Link Between Palm Oil Fatty Acid and Cancer Metastasis

A new study led by researchers at the Institute for Research in Biomedicine (IRB) has discovered how palmitic acid (PA) – a fatty acid often found in palm oil – alters the cancer genome, increasing the likelihood that cancer will spread. Other types of fatty acids, including the omega 6 and omega 9 fatty acids found in foods such as olive oil and flaxseed, have not had this promising effect. The scientists, led by Salvador Aznar-Benitah, PhD, ICREA researcher and head of the IRB Stam Cells and Cancer laboratory, say that while much more research is needed, their results suggest that a diet low in palmitic acid could actually to be effective. in slowing down the metastatic process. Aznar-Benitah is a co-founder of a company that develops antibody therapies aimed at the underlying process, projects that a clinical trial could begin within the next two years.

Reporting on their preclinical research in Nature, the team concluded, “… our findings not only highlight the long-term health risks associated with a PA-rich diet regarding metastatic progression, but also provide mechanical insights to identify new epigenetic and neural / glial-related therapeutic strategies to mitigate and prevent distant spread . ” Their article is titled, “Dietary palmitic acid promotes promising memory with Schwann cells.”

Metastasis, the spread of cancer, remains the leading cause of death in cancer patients and the vast majority of people with metastatic cancer can only be treated, but not cured. There may be different factors that affect metastasis, the authors noted. “Metastatic growth of primary tumors is multifactorial and may depend on non-genetic factors, including lifestyle.” For example, they indicated, high-fat diets promote tumorigenesis in preclinical models of cancer, while obesity has been linked with high aggressiveness of certain types of cancer. Other studies suggest that altered intake and metabolism of fatty acids (FA) lead to cancer progression.

FAs are the building blocks of fat in our body. And although metastasis may be promoted by FAs in our diet, the mechanism responsible is not clear, nor is it known whether all FAs contribute to metastasis. The authors further noted, “The consumption of fatty acids and altered metabolism constitute hallmarks of metastasis, however there is a lack of evidence on the underlying biology, as well as whether all dietary fatty acids are prometastated.”

To address these questions, the team conducted a series of studies, comparing the effects of different FAs, PA, oleic acid (OA), or linoleic acid (LA) on primary tumor formation and on metastasis, in mice. The results showed that PA promoted metastasis in oral carcinomas and melanoma skin cancer, while OA and LA did not have the same effect. None of the tested fatty acids affected the risk of primary tumor formation.

Source: Global Cancer Research

The studies showed that when palmitic acid was supplemented in the diet of mice, it not only contributed to metastasis, but also exerted long-term effects on the genome. Cancer cells that were only exposed to palmitic acid in the diet for a short period of time remained highly metastatic, even when the palmitic acid was removed from the diet. “Tumors from mice that were fed a short-term palm oil-rich diet, or tumor cells that were briefly exposed to PA in vitro remained highly metastatic even after serial transplantation (without further exposure to high levels of PA),” they wrote.

The researchers discovered that this “prometastatic memory” was linked to epigenetic changes that altered the function of metastatic cancer cells and allowed them to form a neural network around the tumor to communicate with cells in their immediate environment and more easily spread. “Our results indicate that dietary PA not only stimulates metastasis, but that it also does so in a long-term stable manner by a transcriptional state that stimulates intratumoral Schwann cells,” they wrote.

The results suggested that the intratumoral Schwann cells activated by metastatic cells exposed to PA adopt what they called a “proregenerative state” linked to the secretion of a specialized extracellular matrix, and when this occurs, it involves communication with neuropeptide, galanin, which that happens. is secreted by CD36 + metastatic cells. “This PA-induced prometastatic memory requires the fatty acid transporter CD36 and is related to the stable clearance of histone H3-lysine 4-trimethylation by the methyltransferase Set1A (as part of the COMPASS complex (Set1A / COMPASS)),” they continued.

Understanding the nature of prometastic cellular communication, the researchers also discovered a way to block it. Aznar-Benitah is a co-founder of start-up ONA Therapeutics, which is developing excellent antibody therapies for metastatic cancer. An initial trial testing a candidate antibody therapy in different forms of cancer is projected to begin within two years.

Aznar-Benitah commented, “I think it is too early to determine what kind of diet could be consumed by patients with metastatic cancer that would slow the metastatic process. That said, based on our results one would think that a diet poor in palmitic acid could to be effective in slowing down the metastatic process, but much more work is needed to determine this … We are not concentrating on this direction of research, instead, we are concentrating on new possible therapeutic goals that we could prevent and that could have a real therapeutic benefit for the patient regardless of their diet.

“If things continue as planned, we could start the first clinical trial in a few years. I am very excited about this and we are investing a lot of effort to generate the best possible therapy from which cancer patients will hopefully be able to benefit in the near future. “

Helen Rippon, PhD, chief executive at Worldwide Cancer Research, which co-funded the reported research, commented, “This discovery is a huge success in our understanding of how diet and cancer are linked and, perhaps more importantly, how we can use this knowledge to start new treatments for cancer. ” Metastasis is estimated to be responsible for 90% of all cancer deaths – nine million deaths a year worldwide, she noted. “Learning more about what spreads cancer and — importantly — how to stop it is the way forward to reduce these numbers. Research on such a discovery is incredibly exciting because it marks the beginning of a journey that will ultimately lead to more lives saved. and more time spent with loved ones.We are all very excited to see the results of this clinical trial and the future impact these findings could have on people with metastatic cancer.

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