Acevedo H F, Hartsock R J
Department of Pathology and Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, MCP-Hahnemann Medical School, Allegheny University of the Health Sciences, Pittsburg, Pennsylvania 15212-9986, USA.
Cancer. 1996 Dec 1;78(11):2388-99. doi: 10.1002/(sici)1097-0142(19961201)78:11<2388::aid-cncr18>3.0.co;2-x.
Investigations using living human cancer cells and the nude mouse model were conducted to evaluate the expression of human chorionic gonadotropin (hCG) in various cancers grown in vitro and in vivo. The aim was to determine whether membrane-associated hCG in any of its forms is a characteristic metastatic marker, and at what levels or ratios.
Human cancer cell lines known to produce tumors that metastasize spontaneously when grown in nude mice (n = 4) were compared with those that do not produce such tumors (n = 4) using analytical (quantitative) flow cytometry. Monoclonal antibodies directed to epitopes of intact hCG (hCG-holo) and its subunits, including beta-human chorionic gonadotropin with its carboxy-terminal peptide (hCG beta-CTP), allowed for the determination of hCG beta-CTP/hCG-holo ratios.
No significant difference in hCG beta-CTP/hCG-holo ratios was found between the cultured human cancer cells that do not metastasize spontaneously (ratio = 2.39) and those that do (ratio = 2.13), and no difference was seen in their growth rate in nude mice. However, the cells isolated from tumors that do not metastasize spontaneously showed a decrease in their ratios to values less than 1. They reverted to their original values after reestablishment in culture and subsequent passages. In contrast, the ratios shown by cells isolated from tumors that metastasize spontaneously increased to 3 to 6 times their original values in culture, then reverted to their original values after reestablishment in culture and subsequent passages.
To our knowledge, these data demonstrate the following for the first time: 1) There is a direct in vivo correlation between human cancer cells that metastasize spontaneously in nude mice and the expression of membrane-associated complete hCG beta (hCG beta-CTP); and the correlation identifies this molecule as a characteristic metastatic phenotype marker. 2) The marked ratio variations under different conditions indicate that the metastatic phenotype is an unstable event. 3) Growth and local invasion in vivo correlates with the expression of hCG-holo.
利用人活癌细胞和裸鼠模型进行研究，以评估人绒毛膜促性腺激素（hCG）在体外和体内生长的各种癌症中的表达情况。目的是确定任何形式的膜相关hCG是否为特征性转移标志物，以及在何种水平或比例下是转移标志物。
使用分析（定量）流式细胞术，将已知在裸鼠体内生长时会自发转移的肿瘤的人癌细胞系（n = 4）与不会产生此类肿瘤的人癌细胞系（n = 4）进行比较。针对完整hCG（hCG-全分子）及其亚基（包括带有羧基末端肽的β-人绒毛膜促性腺激素（hCGβ-CTP））表位的单克隆抗体，可用于测定hCGβ-CTP/hCG-全分子的比例。
在不自发转移的培养人癌细胞（比例 = 2.39）和会自发转移的培养人癌细胞（比例 = 2.13）之间，未发现hCGβ-CTP/hCG-全分子比例有显著差异，并且它们在裸鼠体内的生长速率也没有差异。然而，从不会自发转移的肿瘤中分离出的细胞其比例降低至小于1的值。在重新培养和后续传代后，它们又恢复到原始值。相比之下，从会自发转移的肿瘤中分离出的细胞所显示的比例在培养中增加到其原始值的3至6倍，然后在重新培养和后续传代后又恢复到原始值。
据我们所知，这些数据首次证明了以下几点：1）在裸鼠体内自发转移的人癌细胞与膜相关完整hCGβ（hCGβ-CTP）的表达之间存在直接的体内相关性；并且这种相关性将该分子鉴定为特征性转移表型标志物。2）不同条件下明显的比例变化表明转移表型是一个不稳定的事件。3）体内生长和局部侵袭与hCG-全分子的表达相关。
