In December 2016, (1),(2) this headline accompanied the release of a new study: “Tumor cells are dependent on fat to start metastasis.” The study from Worldwide Cancer Research, a charitable research organization in the United Kingdom, published the findings of Professor Salvador Aznar Benitah, at the Institute for Research in Barcelona (IRB). Here is a summary of those findings:
- A study at IRB Barcelona has identified the cells responsible for initiating and promoting metastasis in several types of human tumors.
- The results show that a protein, CD36, which absorbs fat from the cell membrane, is an essential factor that determines whether tumor cells become metastatic.
- Mice given a high-fat diet developed the most aggressive metastases. The study reports that the metastatic process is enhanced by fat intake.
For IRB Barcelona, the goal will be to co-develop antibodies against CD36 with the potential to treat patients. For today, our goal can be to examine the role of diet and cancer spread.
Cancer cells can manipulate fat to create a protective cocoon against chemotherapy
Not only has it been suggested that fat provides the fuel for cancer metastasis, doctors found that fat can be manipulated by cancer cells to create a protective cocoon against chemotherapy treatments.
In their paper, Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche, (3) researchers at the University of Colorado Anschutz Medical Campus may have found a link as to why obese patients have poorer outcomes in their cancer treatments. It comes down to cancer stem cells manipulating fat stem cells. According to the researchers, “Adipose tissue (fat) has previously been identified as an extra-medullary (inner) reservoir for normal hematopoietic stem cells and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells can utilize gonadal adipose tissue as a niche to support their metabolism and evade chemotherapy.” In the study’s accompanying press release (4) it is explained this way: “researchers found that leukemia stem cells “hide” in fatty tissue, even transforming this tissue in ways that support their survival when challenged with chemotherapy. It is as if leukemia stem cells not only use fatty tissue as a robbers’ cave to hide from therapy, but actively adapt this cave to their liking.”
Epigenetic regulation therapies may break cancer’s use of fat for growth and protection from treatment
Epigenesis is the biological definition of how humans form from a fertilized egg to a multi-organ individual. Cancer also grows through this epigenesis process – mutating and evolving to avoid being killed off by treatments. Therapies that suppress cancer’s abilities to mutate and evolve would be called Epigenetic regulation therapies. Caloric restriction diets and bioactive phytochemicals – spices such as turmeric – would be called weapons of epigenetic cancer targeting.
Caloric restriction diets and bioactive phytochemicals are interventions have been shown to have epigenetic modulatory activities in multiple cancers. Research has suggested that these therapies can decrease the risk of cancer both in preclinical as well as clinical models. Therefore, knowledge of bioactive phytochemicals along with dietary interventions can be utilized for cancer prevention and therapy both alone and with existing drugs to achieve optimum efficacy.
This is not a new idea, a well cited research study from 2003 (5) made these observations on caloric restriction:
- Calorie restriction is the most potent, broadly acting cancer-prevention regimen in experimental carcinogenesis models.
- Translation of the knowledge gained from Calorie restriction research to human chronic disease prevention and the promotion of healthy aging is critical, especially because obesity, which is an important risk factor for several chronic diseases, including many cancers, is alarmingly increasing in the Western world.
1 Tumour cells are dependent on fat to start metastasis. Dec 7, 2016. Access.
2 Pascual G, Avgustinova A, Mejetta S, Martín M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, Bescós C. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017 Jan;541(7635):41.
3 Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M, Gasparetto M, Stevens B, Pei S, Balys M, Ashton JM, Klemm DJ, Woolthuis CM, Stranahan AW, Park CY, Jordan CT. Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche. Cell Stem Cell. 2016 Jul 7;19(1):23-37. doi: 10.1016/j.stem.2016.06.001. Epub 2016 Jun 30. PMID: 27374788; PMCID: PMC4938766.
4 Fatty tissue may be ‘robbers cave’ for cancer stem cells, driving poor prognosis for obese patients Access.
5. Hursting, Stephen D., et al. “Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans*.” Annual review of medicine 54.1 (2003): 131-152.