Dietary conditions affect the invasion and mechanics of engineered tumors*

Tumor growth and progression are influenced by many factors within the microenvironment, including the mechanical properties of the surrounding extracellular matrix, mechanical forces from interstitial fluid pressure (IFP), and the biochemical composition of the interstitial fluid itself. Here, we took advantage of a microfluidics strategy to mimic all three properties simultaneously, which we used to investigate how tumor growth and invasion are influenced by the dietary conditions of the patient. Specifically, we generated avascular 3D engineered tumors comprised of triple-negative human breast cancer cells and used microfluidics to replicate the flow of interstitial fluid at rates observed in vivo. We supplemented human plasma-like medium (HPLM) with additives to mimic five different, commonly observed dietary conditions: normal, ketogenic, post-prandial, high fatty acids, and diabetic. We then cultured the avascular engineered tumors in the presence of each of these different media conditions under flow, and monitored tumor morphology, cell proliferation, and invasion into the surrounding extracellular matrix. Although the morphology and proliferation rates of the cells did not change in response to dietary conditions when cultured in 2D, we found dramatic differences across the dietary conditions when cells were cultured as tumors under flow. We are currently assessing the metabolic profiles of the tumors and media. These results offer valuable insights into the dietary plans beneficial for patients and their potential impact on the effectiveness of cancer treatment.