Ovarian cancer is notoriously difficult to detect early and spreads aggressively. New research from Nagoya University, published in Science Advances, has revealed a key reason why: cancer cells don’t spread alone. Instead, they actively recruit healthy cells lining the abdomen to create pathways for invasion, making the disease far more lethal and resistant to treatment.
The Unexpected Partnership: Cancer Cells and Mesothelial Cells
For years, scientists have struggled to explain why ovarian cancer spreads so quickly, often undetected until it’s too late. The new study shows that ovarian cancer cells leverage the body’s own protective tissues against it. Specifically, they co-opt mesothelial cells – normally benign cells that form a protective lining inside the abdominal cavity.
Researchers found that roughly 60% of cancer cells in abdominal fluid are not floating freely, but are attached to these recruited mesothelial cells, forming hybrid clusters. These clusters aren’t just physically connected; the cancer cells manipulate the mesothelial cells to become invasive agents.
How the Invasion Works: TGF-β1 and Invadopodia
The process begins when ovarian cancer cells release a signaling molecule called TGF-β1. This alters the mesothelial cells, prompting them to grow sharp, spike-like protrusions called invadopodia. These structures act like drills, cutting through tissue and creating pathways for the cancer to spread.
This method of spread is unique: unlike breast or lung cancers which travel through the bloodstream, ovarian cancer largely bypasses blood vessels entirely. Instead, it drifts through abdominal fluid, which has no predictable route. This makes it harder to track and detect early using standard blood tests. The study’s lead author, Dr. Kaname Uno, explains that the cancer cells effectively “manipulate mesothelial cells to do the tissue invasion work.”
Real-Time Observation and Clinical Implications
Researchers were able to observe this process directly in abdominal fluid samples from patients, confirming their findings in mouse models. The implications are significant: current chemotherapy focuses on killing cancer cells, but does not target these assisting mesothelial cells, meaning the cancer can still spread and resist treatment.
The study suggests future therapies could block the TGF-β1 signal or prevent the formation of these hybrid clusters. It also opens the possibility of monitoring these clusters in abdominal fluid as a potential early diagnostic tool.
Ovarian cancer remains the deadliest gynecological cancer, with most patients diagnosed only after the disease has spread. This research finally explains why it advances so fast. By understanding how cancer cells enlist allies, scientists can now focus on disrupting this deadly partnership.
