Breast Cancer TME Model Developed

Penn State researchers have developed a way to three-dimensionally study the relationship between solid, difficult-to-treat tumors and the microenvironment they create to support their growth. The method has the potential to act as a testbed for drugs and other anticancer treatments, according to Ibrahim T. Ozbolat, who led the research. The details of the approach were published in Advanced Biology.

Using metastatic triple-negative breast cancer cells, and specialized modeling techniques, the researchers cultivated tumor microenvironments. "We brought together the tumor and its microenvironment and studied how the embedded tumor affects its surrounding matrix," said Madhuri Dey, first author. "Then we asked if we could get any meaningful genetic information from this composite system."

They found that the physiological changes in tumor behavior—such as growth or movement—are a direct result of cellular communication in the tumor's microenvironment. Cancer cells communicate with endothelial cells that also control the exchange of materials between blood and the extracellular environment.  "The cancer-endothelial cell crosstalk is equally important as the cancer-fibroblast crosstalk," Dey said, noting that each process can influence the other and change how the cancer grows.

To test their approach, the researchers 3D-bioprinted tumor models called spheroids in a microenvironment to see how distance might influence tumor growth. "We asked, 'Can proximity increase cancer aggressiveness?' and we found that there is a critical distance," Dey said. "Tumors far apart don't affect each other, but endothelial cells from neighboring tumors can nourish each other and increase how aggressively the cancer spreads."

Next, the researchers plan to use the fabrication method to investigate how immune cells engineered to target cancer cells can be improved to penetrate solid tumors and limit their spread. "We could also use this as a personalized tool to test treatment effectiveness for individual people—that's a future goal," Ozbolat said. "There are so many ways in which we can apply this tumor microenvironment model."