Johnson B H, Gomi M, Jakowlew S B, Moriwaki K, Thompson E B
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Cell Growth Differ. 1993 Jan;4(1):25-30.
To evaluate possible involvement of a paracrine/autocrine inhibitory growth factor in myeloma cell growth, we studied the expression and actions of two forms of transforming growth factor beta (TGF-beta 1 and TGF-beta 2) on two closely related myeloma cell lines, OPM-1 and OPM-2. Earlier studies showed that both cell lines contain glucocorticoid receptors, but only OPM-2 cells are growth inhibited by dexamethasone (Dex). We found that OPM-2 growth was inhibited by TGF-beta, with TGF-beta 1 exerting a greater effect than TGF-beta 2, and Dex plus TGF-beta 1 acting synergistically. In OPM-1 (Dex insensitive), TGF-beta mRNA was not expressed, whereas it was induced by Dex in OPM-2. It was also possible to block partially the growth inhibition of Dex in OPM-2 cells by the addition of anti-TGF-beta 1 antibodies. These data suggest that the glucocorticoid effect(s) on myeloma cells may be mediated at least in part through modulation of internal and/or external levels of TGF-beta 1.
为评估旁分泌/自分泌抑制性生长因子在骨髓瘤细胞生长中的可能作用,我们研究了两种形式的转化生长因子β(TGF-β1和TGF-β2)在两种密切相关的骨髓瘤细胞系OPM-1和OPM-2中的表达及作用。早期研究表明,这两种细胞系均含有糖皮质激素受体,但只有OPM-2细胞受地塞米松(Dex)抑制生长。我们发现,TGF-β可抑制OPM-2细胞生长,其中TGF-β1的作用强于TGF-β2,且Dex与TGF-β1协同发挥作用。在OPM-1细胞(对地塞米松不敏感)中,未检测到TGF-β mRNA的表达,而在OPM-2细胞中,地塞米松可诱导其表达。此外,通过添加抗TGF-β1抗体,可部分阻断地塞米松对OPM-2细胞生长的抑制作用。这些数据表明,糖皮质激素对骨髓瘤细胞的作用可能至少部分是通过调节TGF-β1的细胞内和/或细胞外水平来介导的。