Researchers from IRB Barcelona have published in the journal ‘Nature’ the details of the mechanism by which palmitic acid in the diet (and not oleic or linoleic acid) favors tumor expansion.
, that is, to the expansion of the primary tumor to other vital organs.
The authors have identified a series of markers of the ‘memory’ left by exposure to: a change that causes cells to maintain a greater metastatic capacity, even months after being exposed to the fatty acid and that could be related to a greater capacity of these tumor cells to innervate.
“In 2017 we published a study pointing out that palmitic acid is correlated with an increased risk of metastasis, but we did not know the mechanism. In this work we detail the process, reveal that there is a ‘memory’ factor of metastatic capacity and point out . It is hopeful ”, explains the study leader, Dr. Salvador Aznar-Benitah.
In this work, oral tumor cells and melanomas from patients have been exposed to a diet rich in palmitic acid and have been shown to have a greater capacity to metastasize in mice, even when this diet is administered for a very short period of time. .
This is due to the fact that the modifications generated by the fatty acid on the genome of metastatic cells (known as epigenetic modifications) are permanent and, consequently, they stably maintain the most “aggressive” properties. The authors describe this behavior as
The results indicate that, even if it occurs in a very early phase of the disease in which the primary tumor may not yet have been detected. Scientists have observed that this expansive and colonizing capacity is acquired due to the consumption of palmitic acid (predominant in palm oil), but not with oleic acid (very abundant in olive oil) or linoleic acid (characteristic flaxseed).
These results suggest that aggressiveness not only has to do with fat metabolism, but also the epigenetic modifications that occur in tumor cells when they ingest palmitic acid.
The innervation of the tumor, key to its expansion
In order for a tumor cell to metastasize, it must first shed the tumor of origin, enter the blood or lymphatic vessels, reach another vital organ, and survive and grow there. In this study, the authors have identified that
The more metastatic tumor cells (ie with a memory) acquire the ability to call the nervous system and the neural network that forms around the tumor generates a regenerative environment, which the cells use for their own benefit, to grow and expand.
One of the key elements in the formation of the neural network that favors metastasis are the so-called Schwann cells, which surround and protect neurons. The work shows that, by blocking Schwann cells, in different ways, the formation of this nerve network is inhibited, and metastasis does not take place.
“This discovery opens up new avenues for research and to specifically avoid cancer metastasis, which is, almost always, where mortality lies ”, concludes Dr. Gloria Pascual, associate researcher at IRB Barcelona’s Stem Cells and Cancer laboratory and co-first author of the article together with Dr. Diana Domínguez.
This work has been carried out using the latest ‘single cell RNA sequencing’ and ‘positional RNA sequencing’ technologies, which have made it possible to characterize in detail the composition of the different cells that make up the tumor. It is one of the first times that the technology of
The study has had the collaboration of the group of Dr. Ali Shilatifard (Feinberg School of Medicine – Northwestern University), who has co-led the work. The laboratories of Doctors Holger Heyn (CNAG-CRG), Ramin Shiekhattar (Sylvester Cancer Center, University of Miami), Coro Bescós (Hospital Vall d’Hebrón) and Neus Prats (Histopathology, IRB Barcelona) also participated.
The project has received funding from Worldwide Cancer Research, the Spanish Association Against Cancer, the Marató de TV3, the BBVA Foundation, the European Research Council, the Generalitat de Catalunya, the Ministry of Science and Innovation of the Government of Spain, the Lilliane Foundation Bettencourt, the “la Caixa” Foundation, the National Cancer Institute and the University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center.
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