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We examined the sensitivity of four human germ-cell-tumor cell lines exhibiting different stages of differentiation to human interferons (IFNs) in vitro. The cell lines were derived from two embryonal carcinomas (NEC 8 and NEC 14), a choriocarcinoma (IMa), and a yolk-sac tumor (HUOT). Treatment with poly I:C induced IFN production in IMa and HUOT cells, but not in NEC-8 and NEC-14 cells. In the two embryonal-carcinoma cell lines, the addition of IFN-alpha, IFN-beta, and IFN-gamma did not prevent infection by vesicular stomatitis virus and encephalomyocarditis virus. Also, in these two lines, 2-5A synthetase was not induced by the addition of IFN-alpha. In contrast, both IMa and HUOT showed sensitivity to the antiviral action of IFN-alpha and IFN-beta against the two viruses, and 2-5A synthetase was induced by IFN-alpha. IFNs added at doses of up to 1000 IU/ml had no antiproliferative effect on NEC 8, NEC 14, and HUOT, whereas colony formation by IMa cells was greatly suppressed by all three forms of IFN. These results indicate that the production of and sensitivity to IFN are developmentally regulated and are related to the level of differentiation of human germ-cell stem cells.

We have studied biologically active substances, tumor angiogenesis factors (TAF), which are supposed to be associated with the proliferation and metastases of choriocarcinoma cells. Eight human choriocarcinoma cell lines were used in the present study. TAF activity was assayed by bioassays using BALB/c mice subcutaneous tissue, chicken chorioallantoic membrane (CAM) and rabbit cornea in vivo and by proliferation of endothelial cells in vitro. 1. We found a positive correlation between the size of tumors developed in xenotransplantation and the number of blood vessels in the tumor tissues. A correlation between the number of blood vessels and TAF activity was also found. 2. With a gel-filtration method, TAF activity was observed in the common fractions in every cell line. The molecular weight of TAF was more than 10,000 daltons. 3. There was a heterogeneity of TAF activity among the cell lines. From these results, it appears that TAF initiates the choriocarcinoma cell-proliferation.

The chick chorioallantoic membrane (CAM) was used as an assay system to examine the invasive potential of human choriocarcinoma cell lines. When 5 X 10(6) cells were inoculated into the CAM at the 10th day of postfertilization, three of eight cell lines formed extensively invasive tumors within the CAM. A tendency to correlation between the tumorigenic potential of cell lines in hamster cheek pouches and their invasive potential in the CAM was noted. In addition, the invasive capacity of cell lines correlated well with the amount of collagenase but did not correlate with the amount of plasminogen activator or cathepsin B secreted by them. It is concluded that a heterogeneity of invasive potential in the CAM exists among human choriocarcinoma cell lines and the role of the collagenase secreted by them is suggested.

The growth of five different kinds of human choriocarcinoma cell lines in vitro was quite alike. However, two distinct types of rapid and slow growth were observed in tumors grown in the hamster cheek pouch. The rapidly grown tumor tissues (BeWo, JEG-3, and NUC-1) involved significantly large numbers of blood vessels per microscopic field, as compared to slowly grown ones (SCH and HM). The vascular response was assayed using cell-free crude tumor angiogenesis factors (TAF) on chorioallantoic membrane (CAM) of the chick embryo. In all cell lines TAF activity correlated well with the extent of tumor growth in vivo. Gel filtration analysis showed that relatively high-molecular-weight (more than 10,000) factors could induce neovascularization in the both assays using CAM and rabbit cornea. These results suggest that a heterogeneity of TAF activity is present among human choriocarcinoma cell lines and tumor growth in xenograft depends on the secretion of TAF by the tumor cells themselves.