Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin
Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin
复制标题
DOI：
10.1016/s0022-5347(01)64369-6
复制
发表时间：
1997-09-01
影响因子：
6.6
通讯作者：
Puri, RK
中科院分区：
文献类型：
--
作者：
Maini, A;Hillman, G;Puri, RK
我们已经在几种实体肿瘤细胞上发现了一种新的细胞表面蛋白，其形式为白细胞介素13受体，包括人肾细胞癌细胞(OBiri等人，1995；Debinski等人，1995)。本研究报告人前列腺癌细胞系也表达高亲和力的IL-13受体(Kd=159 PM)。这些受体之所以具有功能，是因为IL-13意外地促进了所有三种前列腺癌细胞系的增殖，通过胸苷摄取和克隆形成试验确定，前列腺癌细胞系上的IL-13受体被靶向使用由IL-13和突变形式的假单胞菌外毒素(PE38QQR)组成的嵌合蛋白。经蛋白质合成抑制实验表明，IL13-PE38QQR对三种前列腺癌细胞株均有细胞毒作用，IC50在1nmoL/L~15nmoL/L之间，克隆形成实验证实IL13-PE38QR在10nmoL/L时几乎完全抑制集落形成，对表达少量或不表达IL-13R的细胞无细胞毒性。热灭活IL13-PE38QQR对前列腺癌细胞无细胞毒作用，显示其特异性。IL13-PE38QQR在加入毒素前先形成数天，对集落也有细胞毒作用。我们的数据表明，应该进行更多的研究，以靶向携带前列腺癌的IL-13受体。
We have discovered a new cell surface protein in the form of interleukin-13 receptor on several solid tumor cells, including human renal cell carcinoma cells (Obiri et al,, 1995; Debinski et al., 1995). This study reports that human prostate cancer cell lines also express high affinity IL-13 receptors (Kd=159 pM). These receptors are functional because IL-13 surprisingly increased proliferation of all three prostate cancer cell lines studied as determined by thymidine uptake and clonogenic assays, IL-13 receptors on prostate cancer cell lines were targeted using a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE38QQR). This molecule, termed IL13-PE38QQR, has been found cytotoxic to all three prostate cancer cell Lines as determined by the inhibition of protein synthesis, The IC50 ranged between 1 nmol/l. to 15 nmol/l. These data were confirmed by clonogenic assays in which IL13-PE38QQR almost completely inhibited colony formation at 10 nmol/l. IL13-PE38QQR was not cytotoxic to cells that express little or no IL-13R. Heat inactivated IL13-PE38QQR was not cytotoxic to prostate cancer cells indicating specificity. IL13-PE38QQR was also cytotoxic to colonies when they were allowed to form first for several days before the addition of toxins. Our data suggest that additional studies should be performed to target IL-13 receptor bearing prostate cancer.