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Transforming growth factor-beta1: differential effects on multiple myeloma versus normal B cells
M Urashima1, A Ogata, D Chauhan
1Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA.
Blood
|March 1, 1996
Summary
Transforming growth factor-beta1 (TGF-beta1) promotes multiple myeloma (MM) cell growth by upregulating Interleukin-6 (IL-6) secretion and resisting normal B-cell inhibition. This study reveals TGF-beta1
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Interleukin-6 (IL-6) is a critical growth factor for multiple myeloma (MM) cells.
- Bone marrow stromal cells (BMSCs) produce IL-6 and Transforming growth factor-beta1 (TGF-beta1).
- TGF-beta1 can regulate IL-6 secretion in various tissues, including BMSCs.
Purpose of the Study:
- To investigate the role of TGF-beta1 in regulating multiple myeloma (MM) tumor growth in vitro.
- To characterize the production and effects of TGF-beta1 in the context of MM.
- To compare the effects of TGF-beta1 on MM cells versus normal B cells.
Main Methods:
- Quantification of TGF-beta1 secretion by sorted MM cells, peripheral blood mononuclear cells, splenic B cells, and BMSCs.
- Assessment of IL-6 secretion by BMSCs in response to MM cell adhesion and TGF-beta1.
- Evaluation of TGF-beta1's effect on MM cell proliferation and retinoblastoma protein (pRB) phosphorylation.
- Comparison of TGF-beta1's effects on normal B cell proliferation and Ig secretion.
Main Results:
- MM cells and MM-associated BMSCs secreted significantly higher levels of TGF-beta1 compared to normal counterparts.
- TGF-beta1 secretion correlated with IL-6 secretion in MM-BMSCs.
- Anti-TGF-beta1 antibody blocked IL-6 secretion and inhibited IL-6 increase induced by MM cell adhesion.
- Exogenous TGF-beta1 upregulated IL-6 secretion and MM cell proliferation, while inhibiting normal B cell proliferation and Ig secretion.
- TGF-beta1 did not alter or increased pRB phosphorylation in MM cells, contrasting its inhibitory effect on normal B cells.
Conclusions:
- TGF-beta1 is produced by both MM cells and BMSCs, contributing to tumor cell growth.
- MM cells exhibit resistance to the inhibitory effects of TGF-beta1 seen in normal B cells.
- TGF-beta1 plays a significant role in promoting MM progression through IL-6 upregulation and altered cell signaling.
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