Regulation of interleukin-6 secretion from breast cancer cells and its clinical implications

Interleukin (IL)-6 may play possible roles in the proliferation and metastasis of cancer cells, in the development of osteolysis and humoral hypercalcemia, and in the regulation of estrogen production in breast cancer tissues. IL-6 is also suggested to be a cachectic factor in cancer patients. A decrease in serum IL-6 levels induced by medroxyprogesterone acetate (MPA) has been reported to correlate with a reversion of body weight loss in patients with advanced breast cancer. To elucidate the mechanisms of action of the anti-cachectic effect of MPA its effects on IL-6 secretion from the KPL-4 cell line, the first human breast cancer cell line to secrete IL-6 and to induce cachexia, were explored. It has been suggested that an inhibitory effect of MPA on IL-6 secretion from breast cancer cells causes the anti-cachectic effect of MPA. Our other studies have revealed that 5'-fluorouridine (5'-DFUR) inhibits the growth of KPL-4 tumors and decreases IL-6 levels in both serum and tumor tissues. Decreasing serum IL-6 levels resulted in alleviation of body weight loss. Docetaxel increased IL-6 levels in both serum and KPL-4 tumors, but combined treatment with docetaxel and 5'-DFUR resulted not only in a potent antitumor effect but also in a drastic decrease of serum IL-6 levels. In the present paper the possible roles of IL-6 in the development and progression of breast cancer are reviewed, and the regulatory mechanisms of IL-6 secretion from breast cancer cells and the possible clinical implications of decreasing IL-6 secretion by therapeutic agents are discussed.