Taetle R, Payne C, Dos Santos B, Russell M, Segarini P
Department of Medicine, Arizona Health Sciences Center, University of Arizona, Tucson 85724.
Cancer Res. 1993 Jul 15;53(14):3386-93.
Because limited studies examined effects of transforming growth factor (TGF) beta 1 on growth of human acute myelogenous leukemia (AML) cells, we used factor-dependent and primary AML cells to assess TGF-beta 1 effects on human AML cell growth. OCI-AML1 cells were growth inhibited by TGF-beta 1 regardless of which growth factor was used as a stimulus. In contrast, AML-193 cells were resistant to TGF-beta 1 when grown with or without growth factors. UCSD/AML1 cells were sensitive to TGF-beta 1 inhibition when grown with most cytokines but were relatively resistant to TGF-beta 1 in the presence of macrophage colony-stimulating factor (M-CSF). Although cells grown from 5 of 6 AML patients were inhibited by TGF-beta 1, cells from 1 AML patient were growth stimulated by TGF-beta 1 in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, or mast cell growth factor (kit ligand). Thus, 3 growth patterns with TGF-beta 1 were observed: (a) sensitivity to growth inhibition; (b) resistance; and (c) factor-dependent resistance. Further studies showed that AML-193 and UCSD/AML1 cells expressed type II TGF-beta 1 receptors and that ability of TGF-beta 1 to decrease GM-CSF receptors did not correlate with growth inhibition. AML-193 cells and UCSD/AML1 cells grown with M-CSF could be propagated in 1 ng/ml TGF-beta 1, but UCSD/AML1 cells grown with GM-CSF and TGF-beta 1 died. Morphology and agarose gel analysis of DNA showed UCSD/AML1 cells underwent apoptosis when grown with GM-CSF and TGF-beta 1 but not with M-CSF and TGF-beta 1. Similar studies of OCI-AML1 cells showed that TGF-beta 1 induced apoptosis of cells grown in 5637 bladder cell-conditioned medium or GM-CSF. These studies indicate that human AML cells exhibit heterogeneous growth responses to TGF-beta 1 and that some effects of TGF-beta 1 on myeloid cells occur through programmed cell death.
由于仅有有限的研究探讨了转化生长因子（TGF）β1对人急性髓性白血病（AML）细胞生长的影响，我们使用依赖因子的细胞和原代AML细胞来评估TGF-β1对人AML细胞生长的作用。无论使用哪种生长因子作为刺激，OCI-AML1细胞的生长均受到TGF-β1的抑制。相比之下，AML-193细胞在有或无生长因子的情况下生长时，对TGF-β1均具有抗性。UCSD/AML1细胞在与大多数细胞因子共同培养时对TGF-β1抑制敏感，但在巨噬细胞集落刺激因子（M-CSF）存在的情况下对TGF-β1相对抗性。尽管6例AML患者中有5例的细胞受到TGF-β1的抑制，但1例AML患者的细胞在粒细胞-巨噬细胞集落刺激因子（GM-CSF）、M-CSF或肥大细胞生长因子（kit配体）存在的情况下，受到TGF-β1的生长刺激。因此，观察到TGF-β1有3种生长模式：（a）对生长抑制敏感；（b）抗性；（c）因子依赖性抗性。进一步研究表明，AML-193和UCSD/AML1细胞表达II型TGF-β1受体，且TGF-β1降低GM-CSF受体的能力与生长抑制无关。与M-CSF共同培养的AML-193细胞和UCSD/AML1细胞可在1 ng/ml TGF-β1中增殖，但与GM-CSF和TGF-β1共同培养的UCSD/AML1细胞死亡。DNA的形态学和琼脂糖凝胶分析显示，与GM-CSF和TGF-β1共同培养时UCSD/AML1细胞发生凋亡，但与M-CSF和TGF-β1共同培养时不发生凋亡。对OCI-AML1细胞的类似研究表明，TGF-β1可诱导在5637膀胱细胞条件培养基或GM-CSF中生长的细胞凋亡。这些研究表明，人AML细胞对TGF-β1表现出异质性生长反应，且TGF-β1对髓样细胞的某些作用是通过程序性细胞死亡发生的。
