Endothelial cells can regulate the spread of breast cancer

Breast cancer can become lethal once cells leave the primary tumor and develop secondary tumors elsewhere in the body, a process known as metastasis. Before the tumor cells metastasize, they must invade the collagen type I-rich stroma to reach the adjacent blood vessels.

Tan et al. investigated the contributions of the extracellular matrix, tumor metabolism, and blood vessels to cancer invasion.

“In our study, we found that endothelial cells in blood vessels secrete factors that induce breast cancer invasion, which is facilitated by metabolic reprogramming,” said author Matthew Tan.

The researchers used a set of engineering tools that enabled them to develop a breast cancer invasion “on a chip” model. Their approach utilized microfluidic models, computational modeling, and advanced imaging techniques that allowed them to simultaneously measure invasion and cell metabolism.

“We were particularly surprised by how restricting glucose decreased invasion more than directly inhibiting mitochondrial ATP production,” said author Claudia Fischbach. “This indicated that glycolytic metabolism plays a major role in endothelial cell-induced invasion.”

Going forward, the researchers hope to build on the correlation they found between invasion, endothelial cell-secreted factors, and metabolism. Specifically, they hope to uncover what specific molecular mechanisms are at play and if they can target those mechanisms to inhibit endothelial cell-induced invasion.

The approach developed in this study could be useful for modeling any disease where the vasculature may be implicated in modulating other cell types such as Alzheimer’s and pulmonary fibrosis, diseases in which metabolic dysfunction has also been implicated.

Source: “Endothelial cells metabolically regulate breast cancer invasion towards a microvessel,” by Matthew Lee Tan, Niaa Jenkins-Johnston, Sarah Huang, Brittany Schutrum, Sandra Vadhin, Abhinav Adhikari, Rebecca Williams, Warren R. Zipfel, Jan Lammerding, Jeffrey Varner, and Claudia Fischbach, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0171109 .