Researchers identify a natural substance that may limit breast tumor growth.
Researchers at Huntsman Cancer Institute at the University of Utah have found a possible reason obesity may make breast cancer more likely to grow. The study found that fat cells in breast tissue can produce a natural substance that helps destroy damaged or cancerous cells. That protective substance appears in much lower amounts when the fat cells are affected by obesity. The research was led by Keren Hilgendorf, PhD, an investigator at Huntsman Cancer Institute and assistant professor of biochemistry at the University of Utah. Meghan Curtin, a doctoral student in molecular biology, served as the first author. Their findings, published in the journal Science, reveal a new reason to weaken natural breast cancer defense mechanisms in the body.
Breasts contain a large amount of fatty tissue. The fat cells, known as adipocytes, are not all the same. Researchers found that fat cells from lean tissue and fat cells affected by obesity can behave differently around breast cancer cells. One major difference involved a fatty substance called 9S-HODE. The research found that lean fat cells produced much more 9S-HODE than fat cells affected by obesity. The substance helps trigger a natural form of cell death called ferroptosis. This process allows the body to get rid of damaged cells, including some cells that could become cancerous.
When more 9S-HODE was present, breast cancer cells were more likely to die. When less of the substance was available, cancer cells had a better chance of surviving and growing. This finding suggests that obesity may not only create conditions that help cancer grow but may also reduce a natural defense that normally helps keep some cancer cells under control. Researchers tested the finding in laboratory studies and animal models. They also examined breast tissue from human donors. In mouse models with obesity, researchers increased the amount of 9S-HODE produced by fat cells, and this change was linked to slower breast tumor growth.
The results do not mean that obesity directly causes every case of breast cancer. Breast cancer has many known risk factors, and the disease can develop in people of many body sizes. Age, genetics, family history, hormone levels and other factors can also affect a person’s risk. The study does, however, give researchers another way to think about the connection between body fat and cancer. Much of the past research has focused on how obesity may create conditions that help cancer cells survive. The new work suggests that losing substances that normally protect tissue may also play a role.
Researchers said 9S-HODE could eventually become part of a new approach to breast cancer treatment. Because the substance is naturally made by the body, restoring it could potentially bring back some of the protection lost in obese breast tissue. Such treatment is still in the research stage, and additional studies are needed before its safety and usefulness in people can be known. The research team also wants to explore whether fat cells in other parts of the body make 9S-HODE or related substances. If similar activity occurs elsewhere, it could provide information about how obesity affects other types of cancer and other diseases.
The findings add another piece to the growing picture of how body tissue can affect cancer. Cancer cells do not grow in isolation. Surrounding cells and tissues can either support their growth or make survival harder. In breast tissue, the study suggests that healthy fat cells may help create an environment that works against cancer cells. This offers more information that could potentially help support breast cancer prevention.
Sources:
Obesity suppresses natural protection against breast cancer growth
Lean adipocyte oxylipin signaling restrains breast cancer through ferroptosis
Join the conversation!