Diet has an important impact on the plasma, by altering levels of molecules that circulate there. Interstitial fluid is also affected by the same factors.
The biochemical composition (TME) of tumors is altered by these nutrients, which are linked to tumor growth and response to treatment. Their direct effect on cancer cells is still unknown.
Princeton’s team conducted a new study that combined a 3D-microfluidic model of tumor with physiologically appropriate culture media in order to measure the effect of circulating nutrients on tumor growth and invasion as well as overall tumor metabolism.
These findings reveal a startling truth: high-fat diets can lead to breast cancer. High-fat diets also worsen cancer patient outcomes.
The name “cancer” comes from the crab-like appearance of cancer cells. Celeste Nelson is the principal investigator of the study and Wilke Family professor in Bioengineering.
She also teaches chemical and biological engineering. The leading edge of aggressive cancers invades our normal tissue and becomes a lymphatic vessel or blood vessel, escaping to spread.
The team added glucose, insulin or ketones to human plasma-like medium (HPLM), and then added ketones and fats in order to simulate the circulating nutrients of five different dietary conditions, including normal, after eating and diabetic.
Breast cancer cells MDA-MB-231 (triple-negative), were cultured in 2D. Cells looked the same and grew in this condition. In high-fat conditions however, RNA sequencing revealed that genes involved in cell movements and tissue remodeling are more active. The changes were also associated with increased metabolic activity even though there was little difference in the mix of secreted compounds across conditions.
The researchers then cultured the cancer cells in 3D aggregates (called “tumors”) using a microfluidic device that produced interstitial fluid flows similar to those observed in vivo. The tumors were relatively stable across all four diets. When fed with fatty acids or cholesterol, the tumors began to form small hollow extensions, which reached outward.
This is a characteristic of aggressive cancers.
The MMP1 gene was more active, and this helps to break down collagen. The structural changes in tumors were strongly related to this increase.
Nelson says that the MMP1 data jumped out of the data.
Diets high in fat play a major role in promoting gene expression. The environment is degraded, which promotes tumor aggression. This mechanism is not proven yet. Scientists may be able to observe in the future the effect of a high-fat intake on the growth of tumors if the MMP1 is blocked.
Unexpectedly, tumors that were given nutrients designed to simulate a ketogenic (high-fat diet with low carbs), did not appear healthier. These findings are limited but suggest that the ketogenic diet did not provide any clear benefits.
Nelson stated, “We expected a ketogenic to be protective.” We didn’t find that in this study. It tells us that there are a couple of possible explanations.
“One is that a ketogenic dietary regimen could protect against this type of cancer. However, it would work through cells we do not have.”
Ketogenic Diet Protects Early Memory Decline
The tumors were simplified, and did not include many of the complex interactions that occur in the human body. Nelson said that it could also be the case that tumors vary too much to fit into a single research.
Every tumor is unique to the individual. Nelson Said How do you determine when there are enough tumor models that represent the entire patient population? “Maybe that is not possible.”
This study provides a new approach for tumor growth that is more sophisticated than the traditional approaches.
Researchers said that this system was particularly good for identifying the causes of observed effects. This study, for example, suggests that while it has been proven ketogenic diets can slow tumor growth the effects may be due to changes in the environment of the tumor rather than diet. This type of elimination process can reveal new research targets.
Journal Reference
- Maryam Kohram. Carolina Trenado Yuste.
Molly C. Brennan Smith.
Evelyn S. Navarro Salazar. Pengfei Xu. Jasmine E.
Hao. Xincheng Xu. Bharvi Chavre. William Oh. Sherry X. Zhu.
Susan E. Leggett. Rolf Peter Ryseck. Joshua D. Rabinowitz. Celeste M.
Nelson. A 3D microfluidic breast cancer tumor model based on triple-negatives promotes invasion and growth by utilizing fat. APL Bioengineering. DOI: 10.1063/5.0291646
