Kusuhara M, Yamaguchi K, Nagasaki K, Hayashi C, Suzaki A, Hori S, Handa S, Nakamura Y, Abe K
Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1990 Jun 1;50(11):3257-61.
Endothelin (ET)-1 is a vasoconstrictor peptide derived from endothelial cells and now known to be a local regulator of vascular tonus. Recent studies, however, have revealed that ET-1 functions also as growth factor in various cells. By using a specific ET-1 radioimmunoassay, immunoreactive (IR) ET-1, ranging from 4.2 to 150 pM (minimum detectable amount, 4.0 pM), was detected in 13 of 42 human cancer cell lines. The frequencies of IR-ET-1 production and its concentrations were high in mammary, pancreatic, and colon carcinoma cell lines. IR-ET-1 produced by cancer cells possessed the same molecular size as synthetic ET-1 and also had ET-1-like biological activity. Moreover, Northern blot analysis revealed bands corresponding to ET-1 mRNA in cancer cell lines, indicating that IR-ET-1 produced by cancer cells is a product of the ET-1 gene. Since ET-1 in the spent media is present in a sufficient amount to stimulate cellular growth, we sought ET-1 receptors in four pancreatic carcinoma cell lines and human skin fibroblasts. No ET-1 receptors were detected in the pancreatic carcinoma cell lines. However, human skin fibroblasts possessed a large number of ET-1 receptors. This finding raises the possibility that ET-1 produced by cancer cells plays a modulatory role in the growth of stromal cells surrounding cancer cells.
内皮素（ET）-1是一种源自内皮细胞的血管收缩肽，目前已知它是血管张力的局部调节剂。然而，最近的研究表明，ET-1在各种细胞中还具有生长因子的功能。通过使用特定的ET-1放射免疫分析法，在42个人类癌细胞系中的13个中检测到了免疫反应性（IR）ET-1，其范围为4.2至150皮摩尔（最低可检测量为4.0皮摩尔）。在乳腺癌、胰腺癌细胞系和结肠癌细胞系中，IR-ET-1的产生频率及其浓度都很高。癌细胞产生的IR-ET-1具有与合成ET-1相同的分子大小，并且还具有ET-1样的生物活性。此外，Northern印迹分析显示癌细胞系中有与ET-1 mRNA相对应的条带，这表明癌细胞产生的IR-ET-1是ET-1基因的产物。由于用过的培养基中的ET-1含量足以刺激细胞生长，我们在四种胰腺癌细胞系和人皮肤成纤维细胞中寻找ET-1受体。在胰腺癌细胞系中未检测到ET-1受体。然而，人皮肤成纤维细胞拥有大量的ET-1受体。这一发现增加了癌细胞产生的ET-1在癌细胞周围基质细胞生长中起调节作用的可能性。
