Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues.
Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues.
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发表时间：
1992-06
期刊：
影响因子：
11.2
通讯作者：
Steven D. Weitman;R. Lark;L. Coney;Daniel W. Fort;Verna Frasca;Vincent R. Zurawski;B. A. Kamen
中科院分区：
文献类型：
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作者：
Steven D. Weitman;R. Lark;L. Coney;Daniel W. Fort;Verna Frasca;Vincent R. Zurawski;B. A. Kamen
在体外研究的一些上皮细胞中，膜结合叶酸受体启动细胞积累5-甲基四氢叶酸的过程。该受体为GP38，是一种过表达的糖基磷脂酰肌醇锚定糖蛋白，可被两种单克隆抗体识别，分别命名为MOv18和MOv19。利用MOv19免疫印迹、MOv18和MOv19放射免疫测定、Northern印迹分析和放射配体结合（如果可能的话），我们描述了四例尸检中大量正常组织中叶酸受体的有限表达。免疫印迹技术仅检测到40 pg（约1 fmol）的受体蛋白。脉络膜丛中叶酸受体的含量始终最大。其他含有大量受体的组织包括肺、甲状腺和肾脏。肝脏、肠、肌肉、小脑、大脑和脊髓均无免疫反应。叶酸受体基因表达的Northern blot分析证实了这些观察结果。我们还发现一些恶性细胞系比正常上皮细胞或成纤维细胞表达更多的受体。具体来说，恶性细胞结合的叶酸含量大于或等于20 pmol [3H] /10(6)个细胞，而正常上皮细胞和成纤维细胞结合的叶酸含量小于或等于1 pmol /10(6)个细胞。我们还发现6个脑肿瘤中有4个过表达叶酸受体。这些研究揭示了叶酸受体的有限正常组织分布，叶酸受体是一种细胞表面蛋白，可能是开发选择性癌症治疗的有用免疫或药理学靶点。
In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (approximately 1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound greater than or equal to 20 pmol [3H]folate/10(6) cells, while normal epithelial cells and fibroblasts bound less than or equal to 1 pmol radioligand/10(6) cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy.