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Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3883-3888
Hepatocyte Growth Factor (HGF) Induces Interleukin-11 Secretion
From Osteoblasts: A Possible Role for HGF in Myeloma-Associated
Osteolytic Bone Disease
Øyvind Hjertner,
Maria Lyngaas Torgersen,
Carina Seidel,
Henrik Hjorth-Hansen,
Anders Waage,
Magne Børset, and
Anders Sundan
From the Institute of Cancer Research and Molecular Biology,
Norwegian University of Science and Technology, Trondheim, Norway; and
Section of Hematology, University Hospital, Trondheim,
Norway.
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  1 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.
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