How Mutated Cells Transform Their Local Environment So a Tumor Can Develop
Scientists at Memorial Sloan Kettering Cancer Center (MSK) are shedding recent light on a tumor’s earliest moments — revealing how lung cells with cancer-causing mutations recruit accomplices from healthy surrounding tissue to pave the way for a tumor to develop.
This corruption of the local neighborhood — what scientists call the “tumor microenvironment” — begins surprisingly early, as tumors first emerge, according to a study published April 22 in Nature.
The team’s findings show that when this communication with surrounding cells is disrupted, tumors fail to grow.
“We also found that this transformation of the local neighborhood is reversible, if caught early enough. This opens the door to new treatment and prevention strategies,” says study senior author Joo-Hyeon Lee, PhD, a developmental biologist at MSK’s Sloan Kettering Institute.
The research was conducted in mouse models of lung cancer carrying KRAS mutations — one of the most common genetic changes in the disease — as well as in 3D “assembloids,” miniature organs created from mouse and human lung tissue. It was led by first author Erik Cardoso, a doctoral student in Dr. Lee’s lab.
The research builds on Dr. Lee’s previous work studying how healthy lung tissue responds to injury. Normally, when a lung tissue is damaged, specialized stem cells enter a regenerative state where they become flexible so they can replace the damaged cells. Then, once the injury is repaired, they go back to normal.
In the context of early cancer, however, mutated cells hijack this healing response, coaxing neighboring healthy cells to support tumor growth instead of restoring normal tissue.
By understanding how tumors manipulate their microenvironment at the earliest stages, scientists hope to develop interventions that can block this process before cancer becomes established.