CONTROL OF AROMATASE-ACTIVITY IN BREAST-TUMORS - THE ROLE OF THE IMMUNE-SYSTEM

Cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alph a (TNF alpha), have been identified as important regulators of aromata se activity in fibroblasts derived from normal and malignant breast ti ssues, and may play an important role in controlling aromatase activit y in breast tumours. The major source of such cytokines within breast tumours remains to be established but macrophages and lymphocytes, whi ch can infiltrate tumours, have been identified as a potential source of aromatase stimulatory cytokines. To obtain further insight into the possible role played by the immune system in cancer development, and in particular its ability to regulate aromatase activity via cytokine production, we have obtained peripheral blood monocytes and lymphocyte s from an immunosuppressed kidney transplant recipient, receiving cycl osporin A therapy, and a woman with breast cancer. Monocytes and lymph ocytes were stimulated with lipopolysaccharide (LPS), and the conditio ned medium (CM) collected from these cells was tested for its ability to stimulate aromatase activity in fibroblasts derived from normal bre ast tissue from a woman undergoing lumpectomy for the removal of a bre ast tumour. The white blood cell count was lower for the immunosuppres sed patient, mainly because of the reduction in the number of monocyte s and lymphocytes. The ability of CIM from the monocytes and lymphocyt es of the immunosuppressed patient to stimulate aromatase activity was significantly reduced (68% and 82% for monocytes and lymphocytes, res pectively) compared with that of CM from the cells of the woman with b reast cancer. It is possible, therefore, that immunosuppression, which has been found to be associated with a reduction in the incidence of de novo breast cancer in kidney transplant recipients, may exert its e ffect by inhibiting cytokine production by the cells of the immune sys tem and thus oestrogen synthesis. In contrast to the stimulatory effec ts that TNF alpha has on aromatase activity in breast fibroblasts, in MCF-7 breast cancer cells, which possess low aromatase activity, it re duced activity. However, the extent of inhibition of aromatase activit y in these epithelial cells was much lower than the marked stimulation which it can induce in breast fibroblasts. (C) 1997 Elsevier Science Ltd.