Production and regulation of interleukin-11 by breast cancer cells

We have studied the production of interleukin-11 (Il-11) in 13 breast cancer cell (BCC) lines. Two of these cell lines (MDA-MB-231 and Hs578T) expressed the cytokine at both the protein and mRNA levels. Ii-II did not modulate the growth of five BCC lines examined, including the two cytokine-producing BCC lines. The production of Ii-Il was increased by transforming growth factor-pi in a dose-dependent manner with a rapid (2 h) and transient (24 h) mRNA induction, but not by epidermal growth factor, insulin-like growth factor-I and -II, basic fibroblast growth factor, platelet-derived growth factor or parathyroid hormone. The cyclic AMP inducer, forskolin, and the activator of protein kinase C, phorbol 12-myristate 13-acetate, also stimulated the production of Il-11. Besides Ii-II, MDA-MB-231 and Hs578T were the only BCC lines to produce interleukin-6 (Il-6) protein and mRNA. Since Ii-Il and Il-6 are potent stimulators of osteoclast development and bone is a major source of TGF-beta(1), our data suggest that Ii-Il, together with Il-6, contributes to the high bone destructive capacity of MDA-MB-231 cells and could play a role in breast cancer-induced osteolysis. Published by Elsevier Science Ireland Ltd.