Role of thymoma-derived growth factor (MGFF) in growth control of the thymus

BUF/Mna品系的大鼠在两年内自发地发展为大的良性胸腺瘤。肿瘤的高发病率主要由单一易感基因（Tsr-1）调控，并呈显性遗传。胸腺瘤的发生是由于胸腺上皮细胞的异常所致。本研究从大鼠胸腺瘤上皮细胞株TaD-1 - 3的条件培养液中分离纯化出一种刺激胸腺巨噬细胞生长和细胞融合的因子，命名为MGFF。经RCA-琼脂糖凝集素柱层析和SDS-PAGE电泳鉴定，天然MGFF为一种分子量为100 kD的糖蛋白，具有二硫键。MGFF的生物学活性对胰蛋白酶、核糖核酸酶、脱氧核糖核酸酶和各种糖酵解酶具有抗性，并与重组G-CSF、M-CSF和GM-CSF不同。在含有1 mM地塞米松的培养基中建立来自BUF/Mna-rnu/+和BUF/Mna-rnu /rnu大鼠胸腺的克隆上皮细胞系（Dex），并检查生长特性和中间丝的表达。从BUF/Mna-rnu/+（B（nu/+）-5-4）建立的细胞系显示与其它细胞系相似的多边形形状和角蛋白肽的高表达。然而，来自裸大鼠胸腺原基（B（nu/nu）-1-3）的细胞比来自其它细胞系的细胞更平坦且显示出更低的饱和密度。中间丝的表达与其他细胞系有很大不同。这些细胞系可用于研究裸鼠胸腺上皮细胞的缺陷、whn基因的功能以及rnu（whn）基因在BUF/Mna大鼠胸腺瘤发生中的作用。

Rats of the BUF/Mna strain develop spontaneous large benign thymomas in two years. The high incidence of the tumor is regulated mainly by a single susceptible gene (Tsr-1) and is inherited dominantly. An intrinsic thymic epithelial abnormality is responsible for the development of the thymomas. Mice and rats mutated at the nude locus show defects in normal hair growth and thymic dysgenesis.A factor which stimulated the growth and cell fusion of thymic macrophages was produced by a rat thymoma epithelial cell line, TaD-1-3, and designated as MGFF.MGFF was purified from the conditioned medium of TaD-1-3 with DEAE column chromatography, Sephacryl S-200 gel filtration column chromatography, RCA-agarose lectin column chromatography and SDS-PAGE.Native MGFF was suggested to be a glycoprotein of a molecular weight of 100 kdalton, having disulfide-bonds. The biological activity was resistant to trypsin, RNase, DNase and various glycolytic enzymes and distinguished from recombinant G-CSF,M-CSF and GM-CSF.These results suggest that MGFF is a novel factor contributing to the development of the thymoma in a thymoma-prone rat strain, BUF/Mna.Clonal epithelial cell lines from thymuses of BUF/Mna-rnu/+ and BUF/Mna-rnu /rnu rats were established in a medium containing 1 mM dexamethasone (Dex), and were examined for growth characteristics and expression of intermediate filaments. The established cell line from BUF/Mna-rnu/+ (B(nu/+) -5-4) showed a polygonal shape and a high expression of keratin peptides similar to the other cell lines. However, the cells from a nude rat thymic rudiment (B(nu/nu) -1-3) were flatter and showed a lower saturation density than those from the ohter cell lines. Expression of intermediate filaments was much different from other cell lines. These cell lines may be useful in investigating the defects of thymic epithelial cells of nude rats, the function of whn gene and the involvement of the rnu (whn) gene on thymomagenesis in BUF/Mna rats.