O-GLYCOSYLATION OF HCG AND CANCER

人绒毛膜促性腺激素(HCG)由滋养层细胞产生。 妊娠、葡萄胎和绒毛膜癌。这方面和其他方面的研究 实验室已经证明，一种特定的O-连接低聚糖 结构，NeuAcα2，3Ga1β1，3(NeuAcα2，3Gal β1，4GlcNAcβ1，6)GalNAc和N-连接的寡糖 一致发现GlcNAcβ1，4人α1，3三天线型 绒毛膜癌hCG分子。这里的研究表明，这些 在早孕hCG中也可能存在相同的结构，来自 植入后1-3周或滋养层时间 侵袭子宫。这导致了这样的假设：这些 结构是侵袭性细胞的特征。我们的目标 包括： 1)以确认这些结构是 侵袭性细胞的特征，我们将检测碳水化合物 人绒毛膜促性腺激素在妊娠早期及以后的组织结构 睾丸和其他癌症患者。 2)确定这些相同的寡糖是否更丰富 在癌细胞质膜上，它们可能影响细胞-细胞 相互作用和可能的细胞侵袭性。 3)比较相关糖基转移酶活性，GlcNAc β1，6GalNAc转移酶、GlcNAc转移酶-IV和NeuAc 正常和恶性细胞中的α2，3转移酶。 4)滋养层细胞有CSF-I和PDGF受体。最近的实验 提示CSF-I可能促进滋养层细胞早期侵袭 怀孕了。脑脊液-1和血小板衍生生长因子对人绒毛膜促性腺激素糖基化和细胞周期的影响 对滋养层细胞糖基转移酶的活性进行研究。 5)细胞滋养层细胞在很早的时候就以细胞滋养层细胞为主并产生hCG 妊娠，分化的合体结构，然后接管这个 功能。利用培养模型，滋养层细胞的作用 我们将研究hCG糖基化的差异。 6)使用免疫分析和层析聚焦的方法监测 滋养层疾病中“侵袭性细胞”hCG的水平(后续 葡萄胎向恶性疾病的进展)， 早孕(来自持续和自发的妇女- 流产)，以及患有侵袭性胎盘疾病的妇女 (植入性胎盘、植入性胎盘或植入性胎盘)。 7)甲状腺毒症和男性乳房发育症可从侵袭性 绒毛膜癌和睾丸组织中hCG的产生 癌症。以确定“侵袭性细胞”hCG是否改变或 额外的生物活性，类固醇激素，促进cAMP， 促甲状腺激素、受体结合率和代谢清除率 将正常妊娠与“侵袭性细胞激素”进行比较。

Human chorionic gonadotropin (hCG) is produced by the trophoblast in pregnancy, mole and choriocarcinoma. Studies in this and other laboratories have shown that a specific O-linked oligosaccharide structure, NeuAc alpha2,3Ga1 beta1,3(NeuAc alpha2,3Gal beta1,4GlcNAc beta1,6)GalNAc, and N-linked oligosacchrides of the GlcNAc beta1,4Man alpha1,3 triantennary-type are consistently found on choriocarcinoma hCG molecules. Studies here show that these same structures may also be present on early pregnancy hCG, from 1-3 weeks following implantation, or the time of trophoblast invasion of the uterus. This led to the hypothesis that these structures are characteristic of invasive cells. Our objectives are: 1) To confirm the hypothesis that these structures are characteristic of invasive cells, we will examine the carbohydrate structures on further samples of hCG from early pregnancy and from testicular and other cancer patients. 2) To determine if these same oligosaccharides are more abundant on cancer cell plasma membranes, where they may effect cell-cell interaction and possibly cell invasiveness. 3) To compare pertinent glycosyltransferase activities, GlcNAc beta1,6GalNAc transferase, GlcNAc transferase-IV, and NeuAc alpha2,3 transferase in normal and malignant cells. 4) Trophoblast has CSF-I and PDGF receptors. Recent experiments suggest that CSF-I may promote trophoblast invasiveness in early pregnancy. The effect of CSF-1 and PDGF on hCG glycosylation and on trophoblast glycosyltransferase activities will be investigated. 5) Cytotrophoblast cells predominate and produce hCG in very early pregnancy, differentiated sycytial structures then take-over this function. Using culture models, the effects of trophoblast differentiation on hCG glycosylation will be examined. 6) To use immunoassays and chromatofocusing methods to monitor the levels of "invasive cell" hCG, in trophoblast disease (to follow the progression of hydatidiform mole to malignant disease), in early pregnancy (from women having persistent and spontaneously- aborting pregnancies), and in women with invasive placental disease (placenta accreta, increta or percreta). 7) Thyrotoxicosis and gynecomastia can develop from the "invasive cell" hCG production that occurs in choriocarcinoma and testicular cancer. To determine if "invasive cell" hCG has altered or additional biologic activities, the steroidogenic, cAMP-promoting, thyrotropic, receptor-binding and metabolic clearance rates of normal pregnancy and "invasive cell hormone will be compared.