Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG
Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG
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DOI：
10.1016/j.ygyno.2005.12.047
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发表时间：
2006-08-01
影响因子：
4.7
通讯作者：
Kohorn, Ernest I.
中科院分区：
文献类型：
--
作者：
Cole, Laurence A.;Dai, Donghai;Kohorn, Ernest I.
目标。高糖基化hCG （hCG- h）是妊娠着床期和绒毛膜癌时细胞滋养细胞产生的hCG的糖基化变体。我们研究了hCG-H在体外和体内侵袭的生物学功能，以及hCG-H抗体在体内阻断肿瘤发生和肿瘤生长的作用。方法与结果。绒毛膜癌细胞培养液中hCG- h占总hCG免疫反应性的43% ~ 100%，妊娠细胞滋养细胞原代培养液中hCG- h占100%。我们研究了hCG和hCG- h对分离的细胞滋养细胞原代培养物和在基质基膜插入物（评估肿瘤侵袭的培养模型）上培养的3种不同的绒毛膜癌细胞的作用。的;培养基中添加hCG- h可显著促进妊娠和癌细胞源对细胞膜的侵袭，而常规hCG无显著影响。将JEG-3人绒毛膜癌细胞皮下移植到胸腺裸鼠体内。肿瘤迅速形成。13152，小鼠抗hCG-H单克隆抗体和非特异性小鼠IgG（对照），一旦肿瘤清晰可见，每周两次给药。对照组小鼠的生长与时间有相关性（r(2) =0.97），而b152处理小鼠的生长与时间无相关性（r(2) =0.15）。B152阻断肿瘤生长（t检验，IgG vs. 13152, p = 0.003）。在第二个实验中，在绒毛膜癌移植时给小鼠注射抗体B152或IgG。b152显著抑制肿瘤发生（t检验P = 0.0071）。hCG-H是人细胞滋养细胞和人绒毛膜癌细胞体内外侵袭的关键启动子，通过自分泌机制促进肿瘤生长和侵袭。hCG-H是绒毛膜癌细胞侵袭的信号，是一种生物肿瘤标志物。抗hCG-H抗体阻断肿瘤的形成和生长。人或人源化抗hCG-H抗体可能有助于绒毛膜癌和其他妊娠滋养细胞恶性肿瘤的治疗和管理。(c) 2006爱思唯尔公司版权所有。
Objective. HypergIvcosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tunnorigenesis and cancer growth in vivo.Methods and results. hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma cells cultured on Matrigel basement membrane inserts (culture models for assessing tumor invasion). The;Addition of hCG-H to medium significantly promoted invasion of membranes with both pregnancy and cancer cell line sources, while regular hCG had no significant effect.JEG-3 human choriocarcinoma cells were transplanted subcutaneously into athymic nude mice. Tumors rapidly formed. 13152, mouse monoclonal antibody against hCG-H, and non-specific mouse IgG (control) were administered twice weekly once tumors were clearly visible. While a correlation between time and growth was observed with the control group (r(2) =0.97), no correlation was observed with the B152-treated mice (r(2) =0.15). B152 blocked tumor growth (t test, IgG vs. 13152, P-0.003). In a second experiment, antibody B152 or IgG was administered to mice at the time of choriocarcinoina transplantation. B 152 significantly inhibited tumorigenesis (t test P = 0.0071).Conclusions. hCG-H is a critical promoter in human cytotrophoblast and human choriocarcinoma cell invasion in vivo and in vitro, promoting tumor growth and invasion through an autocrine mechanism. hCG-H is a signal for choriocarcinoma cell invasion, making it a biological tumor marker. Antibodies against hCG-H block tumor formation and growth. Human or humanized antibodies against hCG-H may be useful in treating and managing choriocarcinoma and other gestational trophoblastic malignancies. (c) 2006 Elsevier Inc. All rights reserved.