The cholesterol derivative formed in the body has an estrogen-like effect and can stimulate the growth and metastasis of breast cancer, suggests research published in the Science weekly.
Although the experiments were carried out on mice, the authors of the study believe that their results help to better understand why obese women are at greater risk of breast cancer than those who weigh properly. They also indicate that lowering cholesterol – with the help of diet or drugs from the group of the so-called statins – may contribute to the reduction of this risk.
Obesity has been linked in many studies with an increased risk of developing many malignancies, including breast, colorectal and endometrial cancer. Scientists attribute the fact that obese postmenopausal women are more likely to develop breast cancer than lean contemporaries to the fact that adipose tissue produces estrogen, which is the fuel for breast cancer growth. Hormone-dependent tumors account for approx. 70 percent. cases of breast cancer.
In their latest research, US scientists from Duke University in Durham and the University of Texas in Dallas have shown that cholesterol, or rather its metabolite 27-hydroxycholsterol (27HC), which mimics the effects of estrogen in certain tissues, can also drive the growth of breast tumors . This compound acts through the mediation of estrogen receptors and hepatic X-receptors (LXR).
Researchers conducted experiments in genetically altered mice that were predisposed to develop hormone-dependent mammary tumors that metastasize to the lungs. They were injected with one of three compounds – estrogen, 27HC, or placebo. They found that both the female sex hormone and the cholesterol derivative stimulated the growth of tumors.
Conversely, blocking estrogen receptors or LXR receptors slowed their growth.
Moreover, in mice raised from birth on a diet high in cholesterol, breast tumors developed faster, were more aggressive, and metastasized faster. Researchers confirmed that this effect was related to the presence of 27HC and not the cholesterol itself. However, giving rodents a statin drug that inhibited cholesterol synthesis slowed the growth of tumors (as 27HC levels also decreased).
The researchers found that 27-hydroxycholesterol stimulates the growth of hormone-dependent human breast cancer cells by conducting experiments on their cultures. They also observed that 27HC can be produced both by the cancer cells themselves and by specific immune cells (macrophages) that are present in the tumor.
“Taken together, breast tumors have developed a mechanism that allows them to use fuel for growth from a variety of sources,” comments one of the authors of the study, Dr. Donald McDonnell.
His team also noted that the cells of the most aggressive breast tumors produce more of the enzyme that converts cholesterol to 27HC.
“The more dangerous the cancer, the more it produces,” comments co-author Dr. Erik Nelson. The researcher adds that detailed analyzes also suggest that 27HC may contribute to the development of resistance of breast cancer cells to hormonal drugs used in its therapy for many years.
According to the authors of the study, these results indicate that women could in a relatively simple way reduce their risk of developing breast cancer. The key to this is controlling cholesterol levels, which can be achieved through a healthy diet or using statins, which are now taken by millions of people around the world to reduce the risk of heart disease. The researchers also note that this still requires confirmation in the future.
The latest research may also lead to new treatments for breast cancer, such as blocking the enzyme that converts cholesterol to 27HC. (PAP)