A new study, published in the Journal of Clinical Investigation and funded in part by OCRA, has found that mesothelial cells are a critical factor in ovarian cancer metastasis.
High-grade serous ovarian cancer, the most common ovarian cancer subtype, is known to be aggressive, and is associated with the presence of ascites and widespread metastases throughout the peritoneal cavity. The spread can occur when ovarian cancer cells detach from the primary tumor site — typically the fallopian tube — and are carried by peritoneal fluid throughout the peritoneal cavity. The ovarian cancer cells then attach to the mesothelium, a protective layer that surrounds the body’s inner organs, placing them in a new microenvironment within the abdominal and pleural cavity, which includes the lungs and the interior wall of the chest cavity.
Researchers have understood that ovarian cancer preferentially grows on mesothelial-lined surfaces in the abdominal cavity, but further investigation was needed to understand the mechanisms driving this behavior.
In this study, a research team at University of Chicago, which included OCRA grantees Hilary Kenny, PhD, and Ernst Lengyel, MD, PhD, aimed to better understand the role of mesothelial cells — whether they play a passive role, or if mesothelial cells are required for ovarian cancer growth. The team also set out to detect alterations in mesothelial cell gene expression and protein secretion upon interaction with ovarian cancer cells.
Using samples from patients with HGSOC, as well as mouse models, the team found that mesothelial cells are important to the initial stages of ovarian cancer growth in the abdominal cavity. In particular, they determined that mesothelial cells secrete proteins, including ANGPTL4 and STC1, to alter the other “normal” cells in the abdominal cavity, and drive ovarian cancer growth.
“This work, funded by an OCRA Liz Tilberis Award, allowed us to take advantage of multiple tools in the scientific community including lineage tracing mouse models, ablation mouse models, primary cell co-cultures, molecular biology and biochemical techniques to develop new tools to investigate the role of mesothelial cells during ovarian cancer metastasis,” says Dr. Kenny.
“I believe this work is important because we need to ultimately understand the biology of the ovarian cancer tumor microenvironment to ultimately prevent and effectively treat this disease.”
Dr. Hilary Kenny’s grant was made possible, in part, by a generous donation from Ovarian Cancer Alliance of Greater Cincinnati made in memory of Debbie Walter.