Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease.
نویسندگان
چکیده
Multiple myeloma is associated with unbalanced bone remodeling causing lytic bone lesions. Interleukin-11 (IL-11) promotes osteoclast formation and inhibits osteoblast activity and may, thus, be one factor involved in cancer-induced bone destruction. We have previously shown that myeloma cells produce hepatocyte growth factor (HGF). We now report that HGF induces IL-11 secretion from human osteoblast-like cells and from the osteosarcoma cell lines Saos-2 and HOS. In coculture experiments, both the myeloma cell line JJN-3 and primary myeloma cells from 3 patients induced IL-11 secretion from osteoblasts, whereas no induction was observed with the non-HGF producing myeloma cell line OH-2. Enhanced IL-11 induction was observed with physical contact between osteoblasts and myeloma cells as compared with experiments in which contact was prohibited by tissue inserts. Anti-HGF serum strongly reduced the myeloma cell-induced IL-11 secretion. Furthermore, we show that JJN-3 cells express HGF on the cell-surface. Removal of surface-bound HGF on JJN-3 cells reduced IL-11 production induced in cocultures. Transforming growth factor beta1 and IL-1 potentiated the effect of HGF on IL-11 secretion, whereas an additive effect was observed with tumor necrosis factor. Thus, myeloma-derived HGF can influence the bone marrow environment both as a soluble and a surface-bound factor. Furthermore, HGF emerges as a possible factor involved in myeloma bone disease by its ability to induce IL-11.
منابع مشابه
HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma.
The bone disease in multiple myeloma is caused by an uncoupling of bone formation from bone resorption. A key difference between patients with and patients without osteolytic lesion is that the latter have fewer and less active osteoblasts. Hepatocyte growth factor (HGF) is often produced by myeloma cells and is found at high concentrations in the bone marrow of patients with multiple myeloma. ...
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ورودعنوان ژورنال:
- Blood
دوره 94 11 شماره
صفحات -
تاریخ انتشار 1999