METASTATIC PHENOTYPE CORRELATES WITH HIGH EXPRESSION OF MEMBRANE-ASSOCIATED COMPLETE BETA-HUMAN CHORIONIC-GONADOTROPIN IN-VIVO

BACKGROUND. Investigations using living human cancer cells and the nud e mouse model were conducted to evaluate tile expression of human chor ionic gonadotropin (hCG) in various cancers growth in vitro and in viv o. The aim was to determine whether membrane-associated hCG in any of its forms is a characteristic metastatic marker, and al what levels or ratios. METHODS. Human cancer cell lines known to produce tumors that metastasize spontaneously when grown in nude mice (n = 4) were compar ed with those that do not produce such tumors (n = 4) using analytical (quantitative) flow cytometry. Monoclonal antibodies directed to epit opes of intact hCG (hCG-holo) and its subunits, including beta-human c horionic gonadotropin with its carboxy-terminal pep tide (hCG beta-CTD ), allowed for the determination of hCG beta-CTP/hCG-holo ratios. RESU LTS. No significant difference in hCG beta-CTP/hCG-holo ratios was fou nd be tween the cultured human cancer cells that do not metastasize sp ontaneously (ratio = 2.39) and those that do (ratio = 2.13), and no di fference was seen in their growth rate in nude mice. However, the cell s isolated from rumors 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 passa ges. In contrast, the ratios shown by cells isolated from tumors that metastasize spontaneously increased to 3 to 6 times their original val ues in culture, then reverted to their original values after reestabli shment in culture and subsequent passages. CONCLUSIONS. To our knowled ge, these data demonstrate the following for the first time: II There is a direct in vivo correlation between human cancer cells that metast asize spontaneously in nude mice and the expression of membrane-associ ated 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 m etastatic phenotype is an unstable event. 3) Growth and local invasion in vivo correlates with the expression of hCG-holo. (C) 1996 American Cancer Society.