Researchers Show How Tumor’s Location, Environment Affect Its Identity

Using 3-D models of ovarian cancer tumors, scientists found differences in gene activity based on where a cell is in a tumor, demonstrating how a cell’s location and environment in a cancerous tumor can influence which genes are active and the cell’s role in the cancer’s biology. The team, co-led by NCATS researchers, showed that gene activity in cells at or near a tumor’s surface differed from that of cells closer to the tumor center.

This research could yield new clues about how the same diseases can vary in people and progress differently. This work also could help clinicians identify treatment strategies focused on specific areas in tumors, which could lead to better therapies for cancers and other diseases. The team reported its results in Cell Systems.

Researchers used three types of 3-D laboratory models—spheroids, organoids and mouse models—created from human ovarian cancer cells. 

The new system, called Segmentation by Exogenous Perfusion, or SEEP, takes advantage of a dye that diffuses into cells throughout a tumor at a definable rate. Measuring how much dye gets into individual tumor cells provides information on the cell’s location and, specifically, its access to the outside environment. Using computational methods, the researchers linked this information to cells’ gene activity, allowing the scientists to connect the cells’ identities with their location.

“It’s critical to understand that not every cell in a tumor will be exposed to a drug in the same way,” said co-author Dr. Tuomas Knowles of the University of Cambridge. “A cancer drug might kill the cells on the surface of a tumor, but the cells in the middle are different and affected differently. That’s likely contributing to why some therapies fail.”

First author and Harvard University medical student Dr. David Morse said, “Certain tumor cell types are susceptible to certain therapies. Knowing where cells are located and their levels of accessibility in the tumor could help us decide how to use drugs in combination, how long to give a drug and when to move on to other therapies.”