A study led by Nagoya University researchers reports that ovarian cancer cells in abdominal fluid often bind to mesothelial cells—normally part of the abdomen’s protective lining—forming mixed spheroids that invade tissue more efficiently and show increased resistance to chemotherapy. The work was published in Science Advances.
Ovarian cancer is widely considered the deadliest gynecological cancer, in part because it is often diagnosed after it has already spread throughout the abdomen.
A study led by Nagoya University researchers, published in Science Advances, describes a mechanism that may help explain how that spread occurs. The team reports that ovarian cancer cells in ascites—fluid that can accumulate in the abdomen—often travel not as individual cells but as compact spheroids that include mesothelial cells, which normally line the abdominal cavity.
After analyzing abdominal fluid samples from ovarian cancer patients, the researchers found that cancer cells were rarely drifting freely. They estimated that roughly 60% of observed cancer spheroids contained mesothelial cells, forming what the study calls aggregated cancer–mesothelial spheroids.
The study further reports that ovarian cancer cells release the signaling molecule transforming growth factor beta-1 (TGF-β1), which alters associated mesothelial cells. In response, the mesothelial cells develop invadopodia—spike-like structures involved in tissue invasion—helping the mixed spheroids penetrate collagen or mesothelial layers in experimental models.
The researchers describe ovarian cancer’s abdominal dissemination as distinct from cancers that commonly spread through blood vessels. In ovarian cancer, cells can detach from a primary tumor into abdominal fluid, which is moved by breathing and normal body motion, potentially carrying tumor cells to multiple sites within the peritoneal cavity.
Using microscopy on patient samples, along with mouse models and single-cell RNA sequencing, the team reports that mesothelial cells within these mixed spheroids often initiate invasion, while gene-expression changes in the cancer cells themselves were comparatively modest.
Lead author Kaname Uno, identified in the study’s accompanying release as a visiting researcher at Nagoya University’s Graduate School of Medicine, said the findings suggest that cancer cells can "manipulate mesothelial cells to do the tissue invasion work" and then "migrate through the openings" the mesothelial cells create.
The paper also points to potential therapeutic and monitoring approaches, including strategies to interfere with TGF-β1 signaling or to prevent formation of these mixed spheroids. The authors suggest that tracking such hybrid clusters in abdominal fluid could eventually help clinicians monitor disease progression and treatment response, though further validation would be needed before clinical use.
