
Dietary Components That May Cause Cancer to MetastasizeΒ
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Palmitic acid, a saturated fat concentrated in meat and dairy, can boost the metastatic potential of cancer cells through the fat receptor CD36.
The leading cause of death in cancer patients is metastasis formation. Thatβs how most people die of cancerβnot from the primary tumor, but the cancer spreading through the body. βIt is estimated that metastasis is responsible for ~90% of cancer deaths,β and little progress has been made in stopping the spread, despite our modern medical armamentarium. In fact, we can sometimes make matters worse. In an editorial entitled βTherapy-Induced Metastasis,β its authors βprovide evidence that all the common therapies, including radiotherapy, chemotherapy, fine needle biopsies, surgical procedures and anaesthesia, have the potential to contribute to tumour progression.β You can imagine how cutting around a tumor and severing blood vessels might lead to the βmigration of residual tumour cells,β but why chemotherapy? How might chemo exacerbate metastases? βDespite reducing the size of primary tumors, chemotherapy changes the tumor microenvironmentββits surrounding tissuesββresulting in an increased escape of cancer cells into the blood stream.β Sometimes, chemo, surgery, and radiation are entirely justified, but, again, other times, these treatments can make matters worse. If only we had a way to treat the cause of the cancerβs spreading.
The development of antimetastatic therapies has been hampered by the fact that the cells that initiate metastasis remain unidentified. Then, a landmark study was published: βTargeting Metastasis-Initiating Cells Through the Fatty Acid Receptor CD36.β Researchers found a subpopulation of human cancer cells βunique in their ability to initiate metastasisβ; they all express high levels of a fat receptor known as CD36, dubbed βthe fat controller.β It turns out that palmitic acid or a high-fat diet specifically boosts the metastatic potential of these cancer cells. Where is palmitic acid found? Although it was originally discovered in palm oil, palmitic acid is most concentrated in meat and dairy. βEmerging evidence shows that palmitic acid (PA), a common fatty acid in the human diet, serves as a signaling molecule regulating the progression and development of many diseases at the molecular level.β It is the saturated fat that is recognized by CD36 receptors on cancer cells, and we know it is to blame, because if the CD36 receptor is blocked, so are metastases.
The study was of a human cancer, but it was a human cancer implanted into mice. However, clinically (meaning in cancer patients themselves), the presence of these CD36-studded metastasis-initiating cells does indeed correlate with a poor prognosis. CD36 appears to drive the progression of brain tumors, for example. As seen in the survival curves shown below and at 3:21 in my video What Causes Cancer to Metastasize?, those with tumors with less CD36 expression lived significantly longer. It is the same with breast cancer mortality: βIn this study, we correlated the mortality of breast cancer patients to tumor CD36 expression levels.β That isnβt a surprise, since βCD36 plays a critical role in proliferation, migration andβ¦growth ofβ¦breast cancer cells.β If we inhibit CD36, we can inhibit βthe migration and invasion of the breast cancer cells.βΒ

Below and at 3:46 in my video, you can see breast cancer cell migration and invasion, before and after CD36 inhibition. (The top lines with circles are before CD36 inhibition, and the bottom lines with squares are after.)

This isnβt only in βhuman melanoma- and breast cancerβderived tumoursβ either. Now we suspect that βCD36 expression drives ovarian cancer progression and metastasis,β too, since we can inhibit ovarian cancer cell invasion and migration, as well as block both lymph node and blood-borne metastasis, by blocking CD36. We also see the same kind of effect with prostate cancer; suppress the uptake of fat by prostate cancer cells and suppress the tumor. This was all studied with receptor-blocking drugs and antibodies in a laboratory setting, though. If these βmetastasis-initiating cancer cells particularly rely on dietary lipids [fat] to promote metastasis,β the spread of cancer, why not just block the dietary fat in the first place?
βLipid metabolism fuels cancerβs spread.β Cancer cells love fat and cholesterol. The reason is that so much energy is stored in fat. βHence, CD36+ metastatic cells might take advantage of this feature to obtain the high amount of energy that is likely to be required for them to anchor and survive at sites distant from the primary tumourββto set up shop throughout the body.
βThe time when glucose [sugar] was considered as the major, if not only, fuel to support cancer cell proliferation is over.β There appears to be βa fatter way to metastasize.β No wonder high-fat diets (HFD) may βplay a crucial role in increasing the risk of different cancer types, and a number of clinical studies have linked HFD with several advanced cancers.β
If dietary fat may be βgreasing the wheels of the cancer machine,β might there be βspeciο¬c dietary regimensβ we could use to starve cancers of dietary fat? You donβt know until you put it to the test, which weβll look at next.
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