Last Modified: November 1, 2001
Last Updated: 2001-02-07 17:30:40 EST (Reuters Health) - Bone morphogenetic protein (BMP)-4, a member of the transforming growth factor-beta superfamily, inhibits proliferation of multiple myeloma cells and cell lines, according to a report in the January 15th issue of Blood.
In their introduction, the authors explain that bone morphogenetic proteins regulate growth, differentiation, and apoptosis in various cell lines and have been shown to modulate growth and differentiation of hematopoietic stem cells in adult mice. Also, interleukin (IL)-6 induces proliferation and prevents apoptosis of multiple myeloma cells.
Dr. Oyvind Hjertner and colleagues from the Norwegian University of Science and Technology in Trondheim tested the effects of BMP-4 on freshly isolated multiple myeloma (MM) cells and on MM cell cultures and evaluated its influence on IL-6-induced changes in MM cell cultures.
BMP-4 reduced DNA synthesis in IL-6-dependent MM cell lines, but not in IL-6-independent MM cell lines, the researchers report. BMP-4 also induced apoptosis in two IL-6-dependent cell lines. They also found that BMP-4 counteracted the upregulation of Stat3 protein by IL-6 (a possible mechanism of IL-6's anti-apoptotic effects) in the two cell lines tested.
Four of 13 freshly isolated, primary myeloma cell cultures showed >10% loss of viability in response to BMP-4 treatment, the investigators say, and 3 of the 13 cell cultures proliferated in response to IL-6. BMP-4 at least partly counteracted the effects of IL-6 in all three of these latter cultures.
"Our data suggest that treatment with BMP-4 or its analogues should be tried in animal models and possibly in patients with MM," Dr. Hjertner and colleagues conclude. "The activation of BMP receptors may reduce tumor burden and ameliorate bone disease, and it represents a new target for the treatment of this disease."