Laszlo Geder

Evidence for the Association of Cytomegalovirus with Carcinoma of the Prostate

A human genital isolate of cytomegalovirus is shown to have transformed human embryonic lung cells in vitro. These cells produce tumors when injected into athymic nude mice. Two cell lines derived from tissue from human prostatic carcinoma have survived more than 20 passages in vitro and demonstrate cytomegalovirus-specific membrane antigen. Significant humoral antibody titers against cytomegalovirus have been demonstrated. Cell-mediated lymphocytotoxicity against these transformed cells has been demonstrated in patients with urinary tract tumors. This evidence indicates that an association between cytomegalovirus and human prostatic cancer may be more than coincidental.

Establishment and characterization of a new endometrial cancer cell line (SCRC-1).

A new human endometrial cell line, SCRC-1, has been established from a uterine adenocarcinoma. During a period of 57 weeks in culture, the SCRC-1 cells have been passaged over 100 times. Cultures have an epitheloid morphology, high mitotic activity, and a tendency to form multiple cell layers. The cells are polygonal and are arranged in pavement-like fashion. Most have multiple nucleoli, some are multinucleated, and all have heavily vacuolated cytoplasm. Pretreatment with iododeoxyuridine did not reveal viral markers by cocultivation or immunofluorescence techniques. Karyologic studies indicate that the SCRC11 cell line is essentially diploid with a small subpopulation of tetraploid cells. Over a period of 20 weeks, 1 of 14 athymic nude mice inoculated with SCRC-1 cells developed a tumor which histologically closely resembled the original human tumor. Cells were subsequently propagated from this tumor and the resulting epitheloid-like cell line was designated SCRC-1, Tu 1.

Immune response of prostatic cancer patients to cytomegalovirus-infected and -transformed human cells

The indirect immunofluorescence test was used to determine the prevalence of humoral immunity to cytomegalovirus (CMV)‐induced antigens in prostatic cancer patients as compared to age‐matched controls. Significantly more prostatic cancer patients demonstrated high CMV‐antibody titers than did the benign prostatic hyperplasia and nonurogenital cancer groups; however, no significant difference in reactivity was found between patients with prostatic cancer and transitional cell carcinoma of the urinary bladder. When screened against CMV‐transformed human cell lines, the reactivity of the sera followed the rate of expression of CMV‐related antigens of cell lines used in these tests. Cancer 42:1766–1771, 1978.

Lymphocyte Reactivity against Virally Transformed Cells in Patients with Urologic Cancer

Lymphocytes from patients with urologic cancer were tested in microcytotoxicity assays against human cells transformed by cytomegalovirus. Human lymphocytes were significantly cytotoxic against the transformed cell line when compared to a normal human control cell line. Patients with prostatic carcinoma demonstrated greater target cell reduction than those with benign prostatic hyperplasia.

Evidence for nuclear antigens in cytomegalovirus-transformed human cells

THE anti-complement immunofluorescence (ACIF) method has revealed an antigen localised in the nucleus of both producer and nonproducer cultures of lymphoblastoid cells carrying the Epstein–Barr virus (EBV) genome1. Early nuclear antigens resembling the Epstein–Barr nuclear antigen (EBNA) have been detected in human embryo lung (HEL) cells as early as 3 h after infection with human cytomegalovirus (CMV)2. These early antigens could be detected only by ACIF staining. We have reported3 that hamster embryo fibroblasts (HEF) transformed with ultraviolet-inactivated CMV exhibit cytoplasmic and perinuclear CMV-specific antigens when tested with CMV-immune sera in the indirect immunofluorescence (IF) test. We later noted that a human CMV of genital origin established a long-term persistent infection in HEL cells in vitro, which resulted in the development of two transformed cell lines after several cell culture passages4. CMV-specific antigens were demonstrated on the surface of the cells by the indirect IF technique. We have now investigated whether EBNA-like nuclear antigens can be detected in the CMV-transformed human cells with the ACIF technique, and whether there is a correlation of reactivity with early antigens of CMV-infected cells.

Recognition of virally transformed cells by lymphocytes from patients with prostatic cancer.

Data presented describe the first assay using human peripheral blood lymphocytes (PBL) against two unique virally transformed cell lines in vitro. Human cells transformed by a cytomegalovirus (CMV-Mj) isolated from normal human prostate tissue were used as target cells in microcytoxicity assays with lymphocytes from 100 patients. Three target cell types were used: control human embryonic lung cells (HEL), transformed HEL cells (CMV-Mj-HEL-2), and transformed HEL cells retrieved from tumors induced in athymic nude mice (CMV-Mj-HEL-2, T-1) by injection of CMV-Mj-HEL-2 cells. PBL preparations from 84% of all patients tested significantly killed CMV-Mj-HEL-2, T-1 cells. However, only PBL from patients with prostatic carcinoma were cytotoxic for CMV-Mj-HEL-2 cells significantly more often than for control HEL. The implications of this approach are discussed.

Effect of differentiation inducers on growth characteristics of human glioma cell lines.

SummaryThe effect of dimethylsulfoxide (DMSO) and iododeoxyuridine (IUdR) on the growth characteristics of two established human glioblastoma cell lines (FG and HMCN-1) was studied. The FG cell line has been characterized. The HMCN-1 cell line, established in our laboratory, consisted of fibroblastoid and polygonal cells that grew without contact inhibition. Subcutaneous injection of these cells into weanling athymic nude mice induced slowly growing, solid tumors that were histologically spindly with areas that were similar to the original tumor. Chromosomal analyses revealed a human heteroploid pattern with a modal number of 69. The cells of the original human glioma contained S-100 protein and glial fibrillary acidic protein (GFA protein), whereas the established cells failed to express markers. Prolonged treatment of glioma cells with DMSO generated a more adherent, normal human fibroblastoid phenotype that grew with contact inhibition. The new phenotype and proliferative restriction of these cells was evident as late as 50 days after discontinuation of treatment. The chemical induction of cell differentiation resulted in decreased tumorigenic potential in athymic nude mice.