FACTORS PRODUCED BY TERATOMA VARIANTS AND IN VIVO TUMORIGENICITY

小鼠C3H畸胎瘤来源的成脂细胞系1246 在规定的介质中进行脂肪分化的严格要求 胰岛素对这两个过程都有效。几种不同的胰岛素非依赖性细胞系 已经被隔离了。对其中一种名为1246-3A的细菌进行了研究。 1246-3A细胞失去了分化能力，已经成为 致癌的。他们会产生促进增长的活动，这可以刺激 对亲本细胞系1246的生长情况进行了表征。它 发现1246-3A细胞产生胰岛素相关因子(IRF) 类似于胰腺胰岛素，起到自动刺激生长的作用 因子；转化生长因子-α样多肽(55 kDa和15 kDa)；转化生长因子-β样 多肽和一种不同于转化生长因子-α的13 kDa多肽生长因子 和转化生长因子-β。结果表明，转化生长因子-α和β-多肽和 13 kDa组分也抑制了1246细胞的脂肪分化。 根据这些结果，可以认为脂肪 分化抑制剂抑制产生菌的分化 细胞以自分泌的方式存在，可以解释表型的变化 在胰岛素非依赖性突变体1246-3A细胞中观察到。此外，它是 可以假设，生长因子的生产可以对 致瘤性胰岛素非依赖性细胞对较少生长因子的需求 排队。为了研究这些可能性，有几种方法 建议：1)分离高致瘤性胰岛素非依赖性细胞系 来自1246-3A细胞。体外生长特性和体外培养的能力 将对合成内源性生长因子的细胞进行检测和 与1246和1246-3A细胞相比，在细胞和 分子水平；2)表征细胞产生的生长因子 高致瘤性细胞系；3)将亲本细胞系 多种多肽生长因子的表达载体 胰岛素非依赖性细胞系1246-3A(胰岛素、转化生长因子-α、转化生长因子-β) 并在体外检测其生长和分化特性，以及 转基因细胞的体内致瘤特性；4)获得 从胰岛素非依赖性细胞系中获得回复细胞并研究 它们的生长和分化特性，以确定是否 非致瘤特性和分化能力可以恢复。 这项研究将是我们调查的长期目标的一部分。 与描述控制增长的因素的性质有关的 间充质来源细胞系的分化及其生物学特性的研究 作用机制。

Mouse C3H teratoma-derived adipogenic cell line 1246 which grows and undergoes adipose differentiation in defined medium strictly requires insulin for both processes. Several variant insulin-independent cell lines have been isolated. One of them called 1246-3A was particularly studied. 1246-3A cells have lost their ability to differentiate and have become tumorigenic. They produce growth promoting activities which can stimulate the growth of the parent cell line 1246 and which were characterized. It was found that 1246-3A cells produce an insulin related factor (IRF) similar to pancreatic insulin and acting as an autostimulating growth factor; TGF-alpha like polypeptides (55 kDa and 15 kDa); TGF-beta like polypeptide and a 13 kDa polypeptide growth factor different from TGF-alpha and TGF-beta. It was shown that the TGF-alpha and beta polypeptides and the 13 kDa fractions also inhibited adipose differentiation of 1246 cells. Based on these results, it can be suggested that the adipose differentiation inhibitors inhibit the differentiation of the producer cells in an autocrine fashion and can account for the change of phenotype observed in the insulin-independent variant 1246-3A cells. Moreover, it is possible to assume that growth factor production can be responsible for the lesser growth factor requirement of tumorigenic insulin-independent cell line. In order to examine these possibilities, several approaches are proposed: 1) to isolate highly tumorigenic insulin-independent cell lines from the 1246-3A cells. In vitro growth properties and the ability of the cells to synthesize of endogenous growth factors will be examined and compared to the ones of 1246 and 1246-3A cells both at the cellular and molecular levels; 2) to characterize the growth factor produced by the highly tumorigenic cell line; 3) transfect the parent cell lines with expression vectors for the various polypeptide growth factors produced by the insulin-independent cell line 1246-3A (insulin, TGF-alpha, TGF-beta) and examine the growth and differentiation properties in vitro, and tumorigenic properties in vivo of transfected cells, and 4) to obtain revertant cells from the insulin-independent cell lines and investigate their growth and differentiation properties, in order to determine if nontumorigenic properties and ability to differentiate can be recovered. This study will be part of the long-term objective of our investigations related to characterization of the nature of factors controlling growth and differentiation of mesenchymal derived cell lines and understanding their mechanism of action.