Skip to main content
2024 BMES Annual Meeting Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Cancer Technologies

Cancer Technologies - Poster Session E

Poster H5 - Using microfluidics to understand the effects of dietary conditions on triple-negative breast cancer growth and invasion

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  The relationship between diet and the risk of developing cancer has been extensively studied. However, the impact of diet on cancer progression after the formation of a primary tumor remains unclear. Cancer cell metabolism within a tumor is influenced by the nutrients available in the tumor microenvironment, which are partially regulated by diet. Therefore, a patient’s diet could be altered to target specific aspects of tumor metabolism, potentially slowing cancer cell growth and invasion and increasing response to chemotherapy.
Existing methods of cancer cell culture lack key features of in vivo conditions, such as nutrient delivery through interstitial fluid flow. To overcome this limitation, we take advantage of a 3D microfluidic tumor model that mimics the rates of interstitial fluid flow observed in vivo. We use this model to study the effects of diet on the growth of tumors comprised of triple-negative breast cancer (TNBC) cells. We also characterize TNBC cell morphology and growth in 2D culture under different dietary conditions.

Materials and

Methods:  Here, we use MDA-MB-231 human TNBC cells and physiologically-relevant media to study the effects of diet. To recapitulate in vivo conditions, cells were cultured in human plasma-like medium (HPLM) supplemented with additives to mimic five different dietary conditions: baseline, post-prandial, diabetic, ketogenic, and high-fat. To assess whether the different concentrations of metabolites in each media condition affected cell proliferation and nuclear and cell morphology, we carried out EdU analysis and immunofluorescence staining.
To more accurately replicate the flow of interstitial fluid that continually replenishes the metabolites surrounding a tumor, we took advantage of a 3D engineered microfluidic tumor model (Piotrowski-Daspit et al., 2017; Tien et al., 2012) to investigate the effects of the different dietary conditions on tumor growth and cancer cell invasion. Cell proliferation within the tumor was measured using an EdU assay. Tumor morphology and growth were observed every 24 hours for six days with phase-contrast images.

Results, Conclusions, and Discussions: EdU assays of TNBC cells in both 2D culture and the 3D microfluidic model revealed no differences in cell proliferation across dietary conditions. However, we observed that 3D tumors grown in the high-fat condition invaded faster than tumors in the other conditions. Furthermore, hollow regions were observed in the core of tumors in the high-fat condition, indicating cell death and/or migration. These findings suggest a high-fat diet may influence tumor morphology and increase invasiveness, highlighting the potential impact of dietary conditions on tumor progression. Studying the effects of individual dietary components on primary tumor progression could inform further research in mouse models and ultimately help physicians advise patients on how diet can be used to limit cancer progression.

Acknowledgements (Optional):  Bibliography
Piotrowski-Daspit, A.S., Simi, A.K., Pang, MF., Tien, J., Nelson, C.M. (2017). A 3D Culture Model to Study How Fluid Pressure and Flow Affect the Behavior of Aggregates of Epithelial Cells. In: Martin, F., Stein, T., Howlin, J. (eds) Mammary Gland Development. Methods in Molecular Biology, vol 1501. Humana Press, New York, NY.
Tien, J., Truslow, J.G., Nelson, C.M. (2012). Modulation of Invasive Phenotype by Interstitial Pressure-Driven Convection in Aggregates of Human Breast Cancer Cells. PLoS ONE 7(9): e45191.

Acknowledgements
This work was supported in part by grants from the National Institutes of Health (CA187692, CA214292) and the Ludwig Institute for Cancer Research Princeton. JH was supported by the Princeton University MolBio Summer Senior Thesis Fund. MCB was supported in part by a New Jersey Commission on Cancer Research Predoctoral Fellowship (COCR22PRF009). MK was supported in part by the National Science Foundation (through the Center for the Physics of Biological Function PHY-1734030) and the National Cancer Institute (through Rutgers Cancer Institute of New Jersey 1T32CA257957). CT was supported in part by the Damon Runyon Quantitative Biology Fellowship.