(604a) Using Microfluidics to Investigate the Effects of Diet on Tumor Growth and Cancer Cell Invasion

What foods may increase or decrease the risk of cancer? How does diet affect tumor progression or the risk of metastasis? Does a ketogenic diet or post-prandial insulin levels alter the effectiveness of chemotherapy? These questions have been challenging to answer using mouse models or conventional static cell culture models, in which the cancer cells quickly deplete surrounding nutrients. Here, we used a three-dimensional microfluidic system to mimic the interstitial fluid flow present in the tumor microenvironment (TME) in vivo. We combined this system with human plasma-like medium (HPLM) to investigate the effects of normal, post-prandial, and ketogenic diets on tumor growth and cancer cell invasion. Specifically, we used HPLM alone to mimic a normal diet, and supplemented HPLM with insulin or beta-hydroxybutyric acid to mimic post-prandial or ketogenic conditions, respectively. Surprisingly, we found that both ketogenic and post-prandial conditions had effects on tumor growth, measured by tumor area and cell proliferation, and cancer cell invasion in the microfluidic tumor model. To define how these conditions affect cancer cell metabolism, we are using metabolomics to analyze the metabolites present in media flowing from the tumor. By combining physiologically relevant media conditions with a microfluidic tumor model capable of providing a constant flow of nutrients through the TME, our work is uncovering the effects of diet on initial tumor progression. These insights may eventually allow patients to slow the progression of their cancer through diet.