Molecular Diversity and Physiological Roles of Growth Inhibitors

大量证据表明，动物细胞的增殖受到正负向生长刺激之间的平衡调节。为了阐明生长抑制物的分子种类和生理作用，该研究项目的每个成员都研究了存在于不同来源如血清和培养细胞中的细胞抑制蛋白或细胞毒蛋白。从正常兔血清中分离纯化细胞抑制因子和细胞毒因子，并对其进行鉴定。前者是一种耐热、耐酸、抗二硫苏糖醇的蛋白，大小为56 kDa，对多种恶性和非恶性细胞的生长具有可逆性抑制作用。后者以潜伏形式存在于血清中，37℃孵育12h可被激活，从孵育的血清中纯化出两种活性形式，分别为18 kDa和36 kDa。这两种蛋白质对热和酸不稳定，但对二硫苏糖醇耐受，无论细胞类型和恶性程度如何，对啮齿动物细胞都有很强的细胞溶解作用。本研究中表征的其他生长抑制因子包括小鼠新生脑源性抑癌因子(NBCF)、人成纤维细胞分泌的肿瘤退化因子(TDF)、大鼠成胶质细胞分泌的神经母细胞生长抑制因子(NGIF)以及荷瘤小鼠血清中抗肿瘤多糖诱导的肿瘤退化因子(TRF)。

Considerable evidence has accumulated indicating that proliferation of animal cells is regulated by a balance between positive and negative growth stimuli. To clarify molecular species and physiological roles of growth inhibitors, each member of this research project has studied cytostatic or cytotoxic proteins present in different sources such as sera and cultured cells. Both cytostatic and cytotoxic factors were purified and characterized from normal rabbit serum. The former was a heat-and acid-labile but dithiothreitol-resistant protein with 56 kDa, which reversibly inhibited the growth of various malignant and nonmalignant cells. The latter existed in a latent form in the serum and was activated by incubating the serum at 37 ^OC for 12 h. Two active forms with 18 kDa and 36 kDa were purified from the incubated serum. Both proteins, which were heat- and acid-labile but dithiothreitol-resistant, exerted a strong cytolytic effect on rodent cells regardless of cell type and malignancy. Other growth inhibitors characterized in this study include mouse neonatal brain-derived carcinostatic factor (NBCF), tumor-degenerating factor (TDF) secreted by human fibroblasts, neuroblast growth inhibitory factor (NGIF) secreted by rat glioblasts, and tumor-regressing factor (TRF) induced by antitumor polysaccharides in the serum of tumor-bearing mice.