Obesity potently increases the potential for metastasis of ovarian cancer, according to the findings of a new study published in Cancer Research (doi:10.1158/0008-5472.CAN-15-0706). More than 75% of women with ovarian cancer have metastatic disease at the time of diagnosis, resulting in a 5-year survival rate of less than 30%.
Ovarian cancer is a deadly disease that is hard to detect until it has progressed significantly. A large number of studies have shown that higher body mass index (BMI) is associated with a greater risk for ovarian cancer with worse overall survival. More than 35% of women in the United States are obese, putting them at increased risk for the cancer.
However, the influence of obesity on ovarian cancer metastasis had not been evaluated previously. Researchers from the University of Notre Dame and its affiliated Harper Cancer Research Institute (HCRI) in South Bend, Indiana, unveiled important new insights into the relationship between ovarian cancer and obesity.
The researchers noted that ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, and they sought to determine whether obesity contributes to potential for metastasis in ovarian cancer.
“Ovarian cancers metastasize through a distinct mechanism that results in large numbers of lesions anchored throughout the abdominal cavity, making surgery challenging,” said corresponding author M. Sharon Stack, PhD, of Harper Cancer Research Institute.
The research team used an integrative approach combining 3-dimensional cell culture models, tissue explants, and mouse models to evaluate tumor cell adhesion to abdominal mesothelial cells.
“In 3-D tissue culture models, we found that lipid-loading the mesothelial cells, or growing them in the presence of components that make up fat, increased the ability of tumor cells to bind to them,” Stack said.
“As tumor cell-mesothelial cell binding is a key step in ovarian cancer metastasis, this prompted us to study this further in mouse models. We used a ‘diet-induced obesity’ (DIO) protocol in which mice were fed a high fat diet, which was 40% fat, relative to mice fed control chow. When mice were significantly different in weight, they were injected with fluorescent ovarian cancer cells and we monitored metastatic seeding in the abdominal cavity by in vivo imaging.”
Individual organs were removed from the mice and imaged to quantify tumor burden in each organ. Researchers also used another mouse model of obesity termed the ob/ob mouse, which harbored a mutation that caused it to become highly obese.
“In all of these models, we found that obesity enhances ovarian cancer metastatic success,” Stack said.
The study was supported by grants from the National Cancer Institute and the Leo and Ann Albert Charitable Trust and by training fellowships from the National Cancer Institute and the National Science Foundation. Stack also noted the interdisciplinary nature of the research.