TRANSFORMING GROWTH FACTOR BETA IN THE DIFFERENTIATION OF NEUROBLASTOMA AND PNET

在最近的一项免疫组织化学研究中，我们发现缺乏表达 神经母细胞瘤细胞的转化生长因子-β1、2和3，但井除外 神经节神经母细胞瘤和正常组织中分化的神经节细胞 神经节。相比之下，几乎所有原始神经外胚层肿瘤(PNET) 表达不同数量的转化生长因子-β1和3.转化生长因子-β缺失 神经母细胞瘤细胞的条件培养液中也发现有分泌物。 与使用基于转化生长因子-β的生物测定的PNET细胞株形成对比 水貂肺成纤维细胞DNA合成的抑制。这些数据 提示转化生长因子-β在人成纤维细胞分化中的可能作用 神经母细胞瘤。这一假说将在以下内容中进一步探讨 方法：(1)转化生长因子-β的表达和分泌将在 神经母细胞瘤和PNET细胞株分化前后 已知的分化试剂，如维甲酸和TPA。(2)直接 外源性添加转化生长因子-β对未分化和非分化卵巢癌的影响 分化的神经母细胞瘤细胞培养将被确定。(3) 将使用封闭抗体和反义转化生长因子-β寡核苷酸 调节转化生长因子-β对神经母细胞瘤和PNET细胞可能的作用 在试管中。初步数据显示，转化生长因子-β1-mR-NA在SH-B细胞中的诱导。 TPA或TPA处理培养的SY5Y神经母细胞瘤细胞 维甲酸，两者均促进分化。相比之下，IMR- 32个形态分化最小的神经母细胞瘤细胞 与相同药物作用后，细胞内的转化生长因子-β1基因表达水平仅有轻微升高。

In a recent immunohistochemical study, we found lack of expression of TGF-beta1, 2, and 3 by neuroblastoma cells, except for well differentiated ganglion cells in ganglioneuroblastomas and in normal ganglia. In contrast, almost all primitive neuroectodermal tumors (PNET) expressed variable amounts of TGF-beta1 and 3. Absence of TGF-beta secretion was also found in conditioned media from neuroblastoma cell lines, in contrast to PNET cell lines using a bioassay based on TGF-beta inhibition of DNA synthesis in mink lung fibroblasts. These data suggested a possible role of TGF-beta in the differentiation of human neuroblastoma. This hypothesis will be further pursued in the following ways: (1) TGF-beta expression and secretion will be studied in neuroblastoma and PNET cell lines before and after differentiation with known differentiating agents, such as retinoic acid and TPA. (2) Direct effects of exogenously added TGF-beta in undifferentiated and differentiated neuroblastoma cell cultures will be determined. (3) Blocking antibodies and antisense TGF-beta oligonucleotides will be used to modulate possible actions of TGF-beta on neuroblastoma and PNET cells in vitro. Preliminary data have shown induction of TGF-beta1-mRNA in SH- SY5Y neuroblastoma cells following treatment of cultures with TPA or retinoic acid, both of which promoted differentiation. In contrast, IMR- 32 neuroblastoma cells which showed minimal morphologic differentiation with the same agents showed only mild increase in TGF-beta1 mRNA levels.