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One of the most com­mon ingre­di­ents of the human diet might sig­nif­i­cantly accel­er­ate the spread of can­cer cells in the human body while not increas­ing the risk of con­tract­ing can­cer.

A new study pub­lished in Nature sug­gests that palmitic acid might play a spe­cific role in the metas­ta­sis of can­cer cells, such as melanoma or oral car­ci­noma, in patients.

Researchers wrote that while fatty acid uptake is widely cor­re­lated with the devel­op­ment of metas­ta­sis, pre­vi­ous stud­ies did not wholly iden­tify the bio­log­i­cal mech­a­nisms of that process or iden­tify if all fatty acids might be pro-metasta­tic.

The research results also show that the most promi­nent fatty acid in olive oil, oleic acid, has no role in pro­mot­ing any sort of metasta­tic activ­ity. Linoleic acid, another fatty acid found in olive oil and other veg­etable oils, also did not pro­mote metas­ta­sis.

“Previous work in our lab and other labs has shown that a high-fat diet can increase the risk of metas­ta­sis in oral squa­mous cell car­ci­noma and other tumor types,” Gloria Pascual Angulo, a researcher at the stem cells and can­cer lab of the Institute for Research in Biomedicine in Barcelona and co-author of the study, told Olive Oil Times.

“In this study, we have focused on under­stand­ing whether dif­fer­ent fatty acids present in our diet can cause mol­e­c­u­lar changes that increase the risk of can­cer metas­ta­sis,” she con­tin­ued.

“We have iden­ti­fied that dietary palmitic acid, but not other fatty acids like oleic or linoleic, estab­lish epi­ge­netic changes in the tumor cells that result in the inner­va­tion of the tumor and the expres­sion of extra­cel­lu­lar matrix com­po­nents by Schwann cells asso­ci­ated to the tumors,” Angulo added. ​“These tis­sue com­po­nents are used in turn by the tumor cells to spread eas­ily to other organs.”

While the effects of palmitic acid were demon­strated in mice, the researchers used a model that per­fectly cor­re­lates to human biol­ogy.

“We have used in vitro cul­tured cells and in vivo mice mod­els to per­form the stud­ies,” Angulo said. ​“We have worked with ortho­topic xeno­trans­plant mod­els in which we can repro­duce the metasta­tic dis­ease of a patient into an avatar.”

In the case of their exper­i­ment, the avatar is a tumor-bear­ing mouse in which the can­cer cells behave the same as they would in a human patient.

The researchers said that pre­vi­ous clin­i­cal stud­ies in humans had found a cor­re­la­tion between obe­sity and the risk of devel­op­ing can­cer.

“It would be highly prob­a­ble that the dif­fer­ent fats present in a fat diet might oper­ate in the same way as in the ortho­topic xeno­trans­plant mod­els,” Angulo said.

However, the research find­ings do not cor­re­late the con­sump­tion of palmitic acid and palmitic oil to an increased risk of can­cer since the focus of the study was the metasta­tic process.

“Our work is focused exclu­sively on can­cer dis­ease pro­gres­sion, and it could be extrap­o­lated to patients with can­cer in progress,” Angulo said. ​“We have no data about the pos­si­bil­ity that palmitic acid from a palm diet can trans­form healthy cells and con­vert them into tumoral cells.”

According to the researchers, the study results will help deter­mine a bet­ter diet for can­cer patients suf­fer­ing from metas­ta­sis or those at risk of devel­op­ing it.

“Our study indi­cated that the impact of the diet is impor­tant for our body also in the con­text of can­cer and that tumoral cells can use com­po­nents of the diet for their advan­tage, that is, to grow and col­o­nize dis­tant organs,” Angulo said.

While researchers did not explic­itly rec­om­mend most peo­ple elim­i­nate palm oil from their diets, they warned that a bal­anced approach should always be applied when mak­ing food pur­chas­ing and con­sump­tion deci­sions.

“I think that the rel­e­vance of our work has been to iden­tify mech­a­nisms how a fatty diet, and how spe­cific fatty acids, can affect the metasta­tic process to revert it,” Angulo said. ​“It will be very dif­fi­cult to avoid palm oil entirely because it is widely used in the ali­men­tary indus­try, but we can try to avoid over-con­sump­tion of these types of food, espe­cially when there is not a need for it.”

“We can try to bal­ance our diet bet­ter and increase veg­etable intake, but the rea­son is not only due to this study,” she added. ​“Many stud­ies indi­cate that a fatty diet affects the devel­op­ment of dif­fer­ent patholo­gies.”

In the last few years, the global palm oil mar­ket has devel­oped in con­cert with the cau­tion expressed by the sci­en­tific com­mu­nity.

The European Food Safety Authority (EFSA) has for­mally warned the pub­lic about palm oil con­sump­tion since it is a near-ubiq­ui­tous preser­v­a­tive found in many processed foods.

According to data from the Observatory of Economic Complexity, palm oil exports from coun­tries such as Indonesia and Malaysia were val­ued at €26 bil­lion in 2019, mak­ing the com­mod­ity the 126^th most traded prod­uct in the world.

However, oleic and linoleic fatty acids did not behave sim­i­larly to palmitic acid and did not accel­er­ate metas­ta­sis. Researchers indi­cated how tumoral cells exam­ined in vitro were shown to respond dif­fer­ently to dif­fer­ent fatty acids.

“This is because each fatty acid has a dif­fer­ent mol­e­c­u­lar com­po­si­tion and can acti­vate dif­fer­ent and spe­cific sig­nal­ing path­ways in the tumoral cells,” Angulo said.

More specif­i­cally, sci­en­tists found that palmitic acid acti­vates a path­way that depends on the fatty acid recep­tor CD36, which is located on the sur­face of the metasta­tic cell with a high affin­ity for palmitic acid.

“The acti­vated sig­nal­ing of CD36 is related to the mod­i­fi­ca­tion of the tumor stroma that allows the cells to metas­ta­size eas­ily,” Angulo said.

“In sum­mary,” the authors of the study wrote, ​“we pro­vide evi­dence that a dietary metabo­lite induces sta­ble tran­scrip­tional and chro­matin changes that lead to a long-term stim­u­la­tion of metas­ta­sis, and that this is related to a pro-regen­er­a­tive state of tumor-acti­vated Schwann cells.”

Researchers said fur­ther stud­ies would focus on bet­ter under­stand­ing the inner work­ings of the sys­temic com­mu­ni­ca­tion between an aggres­sive tumor, such as a tumor exposed to a high-fat palm diet, and the rest of the organ­ism and how this com­mu­ni­ca­tion can evolve into metasta­tic col­o­niza­tion.

“Additionally, we want to iden­tify the tar­gets that are act­ing in this process and develop clin­i­cal novel ther­a­pies that could treat the metasta­tic process,” Angulo con­cluded.

• Nature
• EFSA