The researchers were particularly interested in how the cancer cells change when the disease metastasizes, since this is when prostate cancer can become lethal. Genetic studies have shown that the loss of PTEN, a tumor suppressor gene, is involved in prostate cancer. About 70% of primary prostate tumors partially lose the PTEN gene. However, the shutdown of PTEN alone does not seem to be the trigger for metastasis.
The team found that another tumor suppressor gene, PML, was usually present in localized prostate tumors, but missing in about one-third of metastatic tumors. In addition, approximately 20% of the metastatic tumors lacked both PTEN and PML.
In tumors missing both the genes, the fat production within the cells changed. The study compared two types of prostate tumors: localized tumors missing only the PTEN gene and metastatic tumors missing both PTEN and PML. They found that the metastatic tumors were producing large amounts of fats, or lipids. The fat could lead to proliferation of the cancer cells, and thus the cancer spreading.
High-fat Western diet
It can be challenging to study prostate cancer in mice, because it is difficult to model metastatic cancer in the animals. However, the researchers switched the mice in their lab from a low-fat, vegetarian diet to a high-fat diet rich in saturated fat, such as is found in food like cheeseburgers and fries. This was meant to simulate a typical Western diet. Once the mice began eating a high-fat diet, tumors missing the PTEN gene rapidly developed into aggressive, metastatic tumors. The change in diet appeared to trigger an effect similar to the loss of the PML gene.
This discovery led the team to test whether an obesity drug could stop the production of fat within the cancer cells. They conducted experiments in the mice and using an obesity drug molecule called fatostatin. The experiment appeared to be successful: the drug blocked the production of fats, and the tumors stopped spreading and even regressed.
Looking ahead, the authors think these findings could help physicians screen prostate cancer patients for the PTEN and PML tumor suppressing genes, which could better identify men at higher risk for developing metastatic cancer. They also hope to find ways for patients whose tumors are missing these genes to reduce the production of fat in the tumors, and thus block the metastatic process, by either making dietary changes or using an obesity drug.
Results from the study were published as papers in the journals Nature Genetics and Nature Communications in January.