Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells.
Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells.
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高度纯化的人 α-凝血酶促进 BALB/c 3T3 细胞的形态转化。
DOI：
10.1093/carcin/13.1.1
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发表时间：
1992
期刊：
影响因子：
4.7
通讯作者：
Carney,DH
中科院分区：
文献类型：
--
作者：
Morris,DL;WardJr,JB;Nechay,P;WhortonJr,EB;Fenton2nd,JW;Carney,DH
纯化的人α-凝血酶刺激磷酸肌苷的转换是其刺激成纤维细胞增殖的必要步骤。由于磷酸肌苷转换释放二酰基甘油，激活蛋白激酶C，我们假设长期暴露于凝血酶可能以类似于长期暴露于磷酯的方式促进细胞转化。目前的研究表明，BALB/c 3T3细胞（亚克隆A31-1-13）长期暴露于凝血酶（5 μg/ml）下，在单层培养中通过诱导病灶确定的形态转化频率比对照增加4- 20倍。这些病灶似乎代表了真正的转化体，因为随机选择的病灶细胞在软琼脂中生长，其饱和密度比对照细胞高2- 3倍。急性凝血酶处理24h后，无论是否有肉豆酸酯佛醇促进，凝血酶的形态转化均有微小但有统计学意义（P< 0.05）的增加，说明凝血酶在本试验系统中可以作为弱引发剂或完全致癌物。低水平的3-甲基胆蒽诱导细胞后，再用凝血酶促进细胞的形态转化（P< 0.005）。因此，凝血酶对体外细胞转化的大部分刺激可能是由于它的促进作用。这些结果提出了组织损伤或慢性刺激后局部释放凝血酶可能在细胞转化和肿瘤发展中发挥作用的可能性，特别是在暴露于初始致癌物致敏的组织中。
Purified human α-thrombin stimulates phosphoinositide turnover as a necessary step in its stimulation of fibroblast cell proliferation. Since phosphoinositide turnover releases diacylglycerol, which activates protein kinase C, we postulated that long-term exposure to thrombin might promote cellular transformation in a manner similar to long-term exposure to phorbol esters, which also activate protein kinase C. The present studies show that chronic exposure of BALB/c 3T3 cells (subclone A31–1–13) to thrombin (5 μg/ml) led to a 4- to 20-fold increase in the frequency of morphological transformation over controls as determined by induced foci in monolayer cultures. The foci appeared to represent true transformants as cells from randomly selected foci grew in soft agar and had saturation densities 2- to 3-fold higher than control cells. Acute thrombin treatment for 24h resulted in small but statistically significant (P< 0.05) increases in morphological transformation with or without promotion by phorbol myristate acetate, indicating that thrombin can act as a weak initiator or complete carcinogen in this test system. Initiation of cells with low levels of 3-methylchoIanthrene followed by promotion with thrombin caused a greater enhancement of morphological transformation (P< 0.005). Thus, it appears that most of the stimulation ofin vitrocell transformation by thrombin may be due to its promotional activity. These results raise the possibility that thrombin released locally following tissue injury or chronic irritation may play a role in cellular transformation and tumor development, especially in tissues sensitized by exposure to initiating carcinogens.