Transforming growth factors produced by normal and neoplastically transformed rat liver epithelial cells in culture.
Transforming growth factors produced by normal and neoplastically transformed rat liver epithelial cells in culture.
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发表时间：
1988-02
期刊：
影响因子：
11.2
通讯作者：
Chientzu Liu;Ming-Sound Tsao;J. Grisham
中科院分区：
文献类型：
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作者：
Chientzu Liu;Ming-Sound Tsao;J. Grisham
研究了正常、化学转化和恶性转化的大鼠肝上皮细胞株分泌转化生长因子(TGFs)α和β的情况。正常培养的WB-F344大鼠肝上皮细胞株不分泌表皮生长因子样活性(推测为转化生长因子-α)，但经N-甲基-N‘-硝基-N-亚硝基处理的WB-F344细胞克隆株，特别是那些高水平表达γ-谷氨酰转肽酶的克隆细胞株，在其条件培养液中分泌转化生长因子样活性。从这些细胞株产生的肿瘤中获得的细胞株分泌转化生长因子-α的能力各不相同，尽管它们都表达高水平的伽马-谷氨酰转肽酶活性。当两个不分泌转化生长因子-α的肿瘤细胞系被移植到同基因大鼠体内时，形成的肿瘤含有高水平的转化生长因子-α样活性。虽然表皮生长因子(也就是转化生长因子-α)在单层培养中抑制了几种肿瘤细胞系的增殖，但这种生长因子经常矛盾地刺激相同细胞系的贴壁非贴壁生长。与转化生长因子-α活性相反，所有细胞株/株都将转化生长因子-β活性释放到其条件培养液中。然而，尽管正常或化学转化的细胞株通常产生非活性形式的转化生长因子-β，但肿瘤细胞系往往会产生活化的转化生长因子-β从头开始。产生活性转化生长因子-β的细胞系的非锚定生长可被转化生长因子-β刺激、抑制或不受影响。被转化生长因子-β抑制的细胞系同时产生转化生长因子-α，这种转化生长因子-α通常能够克服转化生长因子-β的负“自分泌”效应。结论：转化生长因子-α和转化生长因子-β在转化的大鼠肝上皮细胞的生长过程中起着不同的作用。转化生长因子-α对大鼠肝上皮肿瘤细胞系的生长具有明显的正向自分泌作用。在这些转化的上皮细胞系的生长过程中，转化生长因子-β的“旁分泌”效应可能至少与其自分泌效应一样重要。
The secretion of transforming growth factors (TGFs) alpha and beta by normal, chemically transformed, and malignant rat liver epithelial cell lines was investigated. The WB-F344 normal cultured rat liver epithelial cell line does not secrete an epidermal growth factor-like (putatively TGF-alpha) activity, but several clonal cell strains derived from WB-F344 cells which had been treated with N-methyl-N'-nitro-N-nitrosoguanidine, especially those that expressed high levels of gamma-glutamyl transpeptidase, secreted TGF-alpha-like activity into their conditioned media. Cell lines obtained from tumors which were produced by these cell strains varied in their abilities to secrete TGF-alpha, even though they all expressed high levels of gamma-glutamyl transpeptidase activity. When two of the non-TGF-alpha-secreting tumor cell lines were transplanted into isogeneic rats, the tumors that formed contained high levels of TGF-alpha-like activity. Although epidermal growth-factor (hence, TGF-alpha also) inhibited the proliferation of several of these tumor cell lines in monolayer cultures, this growth factor often paradoxically stimulated the anchorage-independent growth of the same cell lines. In contrast to TGF-alpha-like activity, all cell lines/strains released TGF-beta activity into their conditioned media. However, while both normal or chemically transformed cell strains typically produced the inactive form of TGF-beta, the tumor cell lines tended to produce activated TGF-beta de novo. Anchorage-independent growth of cell lines that produced active TGF-beta was either stimulated, inhibited, or unaffected by TGF-beta. Cell lines that were inhibited by TGF-beta concurrently produced TGF-alpha which was usually able to overcome the negative "autocrine" effect of TGF-beta. We conclude that both TGF-alpha and TGF-beta, singly or in combination, are variously involved in the growth of transformed rat liver epithelial cells. TGF-alpha has a predominantly positive autocrine action on the growth of rat liver epithelial tumor cell lines. The "paracrine" effect of TGF-beta may be at least as important as its autocrine effect in the growth of these transformed epithelial cell lines.