Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: A possible role for HGF in myeloma-associated osteolytic bone disease

Multiple myeloma is associated with unbalanced bone remodeling causing lyti c bone lesions. Interleukin-ll (IL-ll) promotes osteoclast formation and in hibits osteoblast activity and may, thus, be one factor involved in cancer- induced bone destruction. We have previously shown that myeloma cells produ ce hepatocyte growth factor (HGF). We now report that HGF induces IL-ll sec retion from human osteoblast-like cells and from the osteosarcoma cell line s Saos-2 and HOS. In coculture experiments, both the myeloma cell line JJN- 3 and primary myeloma cells from 3 patients induced IL-ll secretion from os teoblasts, whereas no induction was observed with the non-HGF producing mye loma cell line OH-2. Enhanced IL-ll induction was observed with physical co ntact between osteoblasts and myeloma cells as compared with experiments in which contact was prohibited by tissue inserts. Anti-HGF serum strongly re duced the myeloma cell-induced IL-ll secretion. Furthermore, we show that J JN-3 cells express HGF on the cell-surface. Removal of surface-bound HGF on JJN-3 cells reduced IL-ll production induced in cocultures. Transforming g rowth factor pi and IL-1 potentiated the effect of HGF on IL-ll secretion, whereas an additive effect was observed with tumor necrosis factor. Thus, m yeloma-derived HGF can influence the bone marrow environment both as a solu ble and a surface-bound factor. Furthermore, HGF emerges as a possible fact or involved in myeloma bone disease by its ability to induce IL-11. (C) 199 9 by The American Society of Hematology.