Morimasa Sekiguchi

Prostaglandin D2 inhibits the proliferation of human malignant tumor cells

The cytotoxic effect of prostaglandin (PG) D2, PGE1 and PGF2 alpha was examined on human osteosarcoma cells (KSu cell line) in vitro, and PGD2 was most effective. DNA, RNA and protein syntheses of KSu cells were also found to be inhibited by PGD2 at a concentration of 5 micrograms/ml. Furthermore, the proliferation of various human malignant tumor cells was inhibited by PGD2 without exception so far. These results suggest that PGD2 shows an anti-neoplastic effect on a variety of human malignant tumor cells.

HUMAN TESTICULAR GERM CELL TUMORS IN VITRO and IN ATHYMIC NUDE MICE

Four cell lines derived from pure and mixed types of human testicular germ cell tumors in vitro and in nude mice were examined by light and electron microscopies. The NEC8 and NEC15 cell lines in vitro were composed of embryonal carcinoma cells with potentiality of trophoblastic differentiation. All of the tumors formed in nude mice by both cell lines were pure embryonal carcinomas. On the other hand, the NEC14 and ITO‐II cell lines showed morphological differentiation from embryonal carcinoma cells to trophoblastic cells and to yolk sac tumor cells in vitro. In nude mice, these cell lines formed mixed tumors which consisted of embryonal carcinoma, yolk sac tumor, immature teratoma or trophoblastic cells. Our data suggest that some embryonal carcinomas have multipotentiality of morphological differentiation but that others have little such potentiality.

PRODUCTION OF ALPHA‐FETOPROTEIN BY HUMAN GERM CELL TUMORS IN VIVO AND IN VITRO

The production of alpha‐fetoprotein (AFP) by human germ cell tumors was studied in surgical specimens, cultured cells and transplanted tumors in nude mice. AFP was detected most frequently in yolk sac (endodermal sinus) tumors, and it was also detected, though only occasionally, in embryonal carcinomas and in teratomas. AFP‐positive cells in teratomas presented a glandular or hepatoid appearanece. Our experimental data suggest that AFP production in embryonal carcinomas is due to the functional expression of yolk sac differentiation preceding its morphologic expression. Although the transplanted tumors maintained the productivity of AFP, the cultured cells were not successful in maintaing a continuous AFP production.

Alpha-fetoprotein-producing gastric carcinoma: Biological properties of a cultured cell line

We describe a gastric carcinoma cell line that has been maintained in vitro for more than 10 years and retains the capacity to produce a large amount of alpha-fetoprotein. This cell line was isolated from a metastatic lymph node of a 63-year-old male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed high serum levels of alpha-fetoprotein. The primary tumor was moderately differentiated tubular adenocarcinoma and the lymph node was poorly differentiated adenocarcinoma without any particular pattern. The cultured cells grew as densely packed islet-like colonies with small polygonal cells. Electron microscopy revealed cells abundant in cytoplasmic organelles, with some cellular attachments being tight with junctional complexes and some being loose across intercellular spaces. The free cell surface had microvilli. The population doubling-time was 152 h at passage 58. Chromosomal analysis revealed the modal number to be 77, with numerous karyotype abnormalities. The tumorigenicity of the cultured cells in athymic nude mice was positive only when they were subcutaneously transplanted beneath a plastic plate, but when the cells were transplanted subcutaneously or administered by intrasplenic injection in intact or weakly irradiated nude mice, no tumorigenicty was shown. The cell line produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic antigen, and tissue polypeptide antigen. This cell line may be useful for comparative studies of different types of gastric carcinoma and alpha-fetoproteins of different origins.

PRODUCTION OF β-HUMAN CHORIONIC GONADOTROPIN BY GERM CELL TUMORS IN VIVO AND IN VITRO

Production of the β‐subunit of human chorionic gonadotropin (β‐hCG) by human germ cell tumors was studied in surgical specimens, cultured cells and xenografted tumors. β‐hCG was identified most frequently in the syncytiotro‐phoblastlc and intermediate trophoblastic components of choriocarcinoma, and it was also detected in syncytiotrophoblastic giant cells, occasionally in association with embryonal carcinoma, and less frequently with yolk sac tumor, seminoma and dysgerminoma. Our experimental data suggest that β‐hCG production by syncytiotrophoblastic giant cells in association with embryonal carcinoma is a result of trophoblastic differentiation of embryonal carcinoma. Moreover, it was proved that the production of β‐hCG by human embryonal carcinomas is regulated by more factors than is the case for human choriocarcinomas.

Differential production of interleukin 6 in human osteosarcoma cells and the possible effects on neoplastic bone metabolism

SummaryInterleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. We have investigated the effects of IL-6 produced by human osteosarcoma cells on tumor cells from two clonal human osteosarcoma cell lines, KSU.C3 and NOS-1.C8. We were unable to identify any effects of IL-6 such as cell proliferation, alkaline phosphatase activity, osteocalcin production, or collagen synthesis on the bone-forming phenotypes. However, the KSU.C3 cell line, which showed a little osteoid and no bone formation and was accompanied by a few osteoclasts in the xenografted tumors, produced high levels of IL-6, the production of which was quickly and easily stimulated by various agents. On the other hand, the NOS1.C8 cell line, which formed abundant osteoid or bone and was accompanied by no osteoclasts in the xenografted tumors, produced no detectable levels of IL-6 without stimulation, and the production of IL-6 in response to IL-lβ was slower. Our data suggest that IL-6 produced by osteosarcoma cells does not play an important role in bone formation, but may mediate osteoclastic bone resorption.

Origin of human neuroblastoma cell lines TGW and TNB1

Analysis of DNA rearrangements and N-myc gene amplification was reported by H. Kato and associates in the July 1989 issue of this journal [I]. They used three human neuroblastoma cell lines, IMR-32, TGW and GOTO. TGW (also designated TOG [2]) was established as a cell line by one of us (M.S.) in May 1979 from a human neuroblastoma in nude mice. It originated from an autopsy specimen of a 23-monthold Japanese boy with disseminated neuroblastoma who died on April 28, 1977 [3]. The tumor in nude mice was later called ‘TNBl xenograft’ in our laboratories due to the rapid increase in number of human tumors in nude mice. In December 1983, this xenograft was given to another investigator in our group (N.K.) as in vivo material of human neuroblastoma, who also succeeded in culturing this material in vitro. Since then, the tumor in nude mice and the new cell line have both been referred to as TNB 1, and the name TNB 1 has appeared in several publications [4-91. Cytogenetic and some molecular cytogenetic characteristics of both the first and the second cell line were recently studied again. Representative karyotypes are: