The current study was designed to test the hypothesis that melatonin inhibits estrogen production in breast adipose fibroblasts and alters their interaction with malignant epithelial breast cells. Fibroblasts are a type of connective tissue cell whose main function is to maintain the structural integrity of connective tissues. Breast adipose (fat tissue) fibroblasts have important interactions with estrogen-dependent tumor cells. The human breast gland consists of a branching ductal-lobular system lined by epithelial cells (in which milk production occurs). Breast cancer arises most often in these mammary gland epithelial cells. Accumulations of adipose fibroblasts around malignant epithelial breast cells provide structural and biochemical support for breast cancer. The fibroblast component of breast tissue is also an important source of estrogen for postmenopausal women.
To conduct the study, the authors cultured both normal breast adipose fibroblasts and breast cancer-associated fibroblasts. The normal cells were obtained from women undergoing breast reduction surgery, while the cancer-associated fibroblasts were isolated from three women with estrogen receptor positive (ER+) invasive ductal tumors. The fibroblasts were treated with melatonin. Physiological doses of melatonin (such as produced naturally in the body) were shown to interfere with stimulation of CYP19A1 expression and aromatase activity (the CYP19A1 gene encodes the aromatase enzyme). The authors conclude that lower levels of melatonin in aging women may increase the risk of ER+ breast cancer through a decreased ability to suppress CYP19A1 expression and subsequent estrogen production within the breast.