WASHINGTON – A high-fat diet accelerates the growth and spread of triple-negative breast cancer tumors, according to a new study conducted by researchers at Princeton University. The findings, published today in APL Bioengineering, challenge previous assumptions about the role of diet in cancer progression and suggest that dietary fat may be more impactful than glucose, insulin, or ketone levels in this aggressive form of the disease.
The research team, led by Celeste M. Nelson, engineered a novel tumor model using a human plasmalike medium to mimic the complex biochemical environment surrounding tumors in the body. This allowed them to isolate the effects of specific nutrients and observe how cancer cells metabolically reprogram themselves under different dietary conditions.
“We took the approach of building identical engineered tumors and culturing them in conditions that mimic the blood composition of patients under different dietary states,” Nelson said. “We were hoping to identify dietary conditions that would leisurely tumor growth. Instead, we found one dietary condition – a high-fat diet – that sped up tumor growth.”
Triple-negative breast cancer, which accounts for approximately 10-20% of all breast cancer cases, is particularly difficult to treat due to the fact that it lacks the receptors that typically respond to hormone therapy. This necessitates more aggressive treatment options, and the Princeton study suggests that diet could be a crucial factor in treatment efficacy.
The researchers examined the impact of four different dietary conditions – high-insulin, high-glucose, high-ketone, and high-fat – on tumor structure, growth, and spread. They discovered that a high-fat diet not only accelerated tumor growth but also increased levels of the enzyme MMP1. MMP1 degrades the extracellular matrix, the network of proteins surrounding cells, and is associated with a poorer prognosis for cancer patients.
Previous studies examining the link between diet and tumor growth have often fallen short due to their inability to replicate the complexity of the human body, researchers noted. The interplay between the immune system, metabolic tissues, and the microbiome all influence cancer cell behavior. Earlier research struggled to accurately simulate the constant flow of nutrients around cells, which occurs in interstitial fluid.
“Cells are typically cultured in media that is saturated with sugars and other biochemicals at levels that don’t match what you see in the human body,” Nelson explained. “Our study shows that tumor cells behave differently when cultured in media that matches the biochemical composition of human plasma.”
The Princeton team plans to build on these findings by investigating how different dietary conditions affect the response of tumors to chemotherapy. “We plan to grab the same system and define whether tumors respond differently to chemotherapy when cultured in media mimicking the different dietary conditions,” Nelson said. “This would allow physicians to potentially make recommendations about what a patient should eat if prescribed a specific therapy.”
The study, titled “Fat promotes growth and invasion in a 3D microfluidic tumor model of triple-negative breast cancer,” was authored by Maryam Kohram, Carolina Trenado-Yuste, Molly C. Brennan-Smith, Evelyn S. Navarro Salazar, Pengfei Zhang, Jasmine E. Hao, Xincheng Xu, Bharvi Chavre, William Oh, Sherry X. Zhang, Susan E. Leggett, Rolf-Peter Ryseck, Joshua D. Rabinowitz, and Celeste M. Nelson. The research is available at https://doi.org/10.1063/5.0291646.
