Targeting support cells to stop triple-negative breast cancer in its tracks

A new study co-led by Morag Park, Ph.D., Rosalind and Morris Goodman Cancer Institute (GCI) Investigator and Director, and Christopher Moraes, Ph.D., Associate Member at the GCI, in collaboration with Jiannis Ragoussis, Ph.D., reveals important insights into the role of cancer-associated fibroblasts (CAFs) in the spread of triple-negative breast cancer.

Although CAFs are not cancerous themselves, they are known to support tumor growth and help cancer cells invade other tissues. In this study, the team isolated CAFs from human triple-negative breast tumors and developed a culture system that mimics the mechanical stiffness architectures found in early-stage tumors.

The researchers found that CAFs from patients with metastatic cancer were highly invasive, moving through the system regardless of its stiffness. In contrast, CAFs from non-metastatic tumors only became invasive when exposed to stiff tissue conditions—similar to those seen in more advanced tumors.

A major finding of the study was the identification of the aryl hydrocarbon receptor (AhR) as a key driver of CAF invasiveness. Elevated AhR levels were consistently found in the more aggressive CAFs, and the team demonstrated that AhR is both necessary and sufficient to trigger invasive behavior in these cells, promoting cancer progression.

This work introduces a new model for studying CAF activity, provides tools for better patient stratification, and identifies AhR as a potential therapeutic target to reduce metastasis in triple-negative breast cancer.

By exploring every dimension of cancer biology, we continue advancing toward the goal of #knowledgetocure.