ATLAS Enables Scalable Modeling of Metastasis

Metastasis, the spread of cancer from a primary tumor to distant sites in the body, is difficult to investigate because it is hard to recreate the conditions circulating cancer cells experience in the bloodstream. Rice University bioengineers have introduced the Advanced Tumor Landscape Analysis System (ATLAS), a platform that simplifies one of the major obstacles in this research by enabling the production of large numbers of cancer cell clusters that accurately model those involved in metastasis. Using ATLAS, the team identified mechanisms that help cancer clusters survive as they circulate during the metastatic process.

Developed in the lab of Michael King, ATLAS extends earlier efforts that used superhydrophobic, or strongly water-repelling, surfaces. When droplets containing cells are placed on such surfaces, they bead up rather than spread, prompting cells to adhere to one another and form three-dimensional clusters. “Metastasis is still poorly understood because adequate laboratory techniques to recreate this complex process are lacking,” said King. 

The King lab has pursued high-throughput methods to create cancer cell clusters for years, either composed solely of cancer cells or mixed with stromal cells that commonly occur in the tumor microenvironment. To examine metastatic behavior, these cluster models are subjected to conditions that closely approximate those in the body, including animal models and blood flow experiments. ATLAS improves on previous approaches by reducing both time and cost, relying on 3D-printed microwell arrays treated to reproduce the nanoscale water-repelling effect seen on natural surfaces like lotus leaves.

“The way this is achieved, both in nature and in the laboratory, is to create a surface that is rough on a nanoscale level, and then to coat the nanoscale bumps with a nonwetting substance such as Teflon or wax,” said Alexandria Carter, first author on the study published in Advanced Healthcare Materials. “Here, we achieved this for the first time through 3D printing, which means the method is scalable and easily adoptable by other labs.”

The researchers applied ATLAS to generate clusters of prostate cancer cells, including clusters containing cancer-associated fibroblasts (CAFs), a type of stromal cell. Tests showed that clusters traveling together, especially those with CAFs, were more likely to withstand the stresses of circulation and continue growing. “One of the most exciting elements of our paper is that it does not just report on a new experimental method for other researchers to use, but it also reports new fundamental biological results,” Carter said. She added, “Perhaps in the future the next generation of prostate cancer drugs will target these CAF ‘escorts’ as a way to prevent metastasis.”