For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.

https://cancerres.aacrjournals.org/content/canres/48/3/589.full.pdf

Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay

Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells. This stimulation is the most rapid transcriptional response to peptide growth factors yet described, and implies a role for c-fos in cell-cycle control. Transformation by c-fos may result from a temporal deregulation of this control.

Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene

Antibodies to human t-lymphotropic virus type-i in patients with tropical spastic paraparesis

Head and neck cancer.

We have reconstituted a matrix of basement membrane onto a filter in a Boyden chamber and assessed the ability of various malignant and nonmalignant cells to penetrate through the coated filter. Cells from all the malignant cell lines tested were able to cross the matrix in 5-6 h, whereas human fibroblasts as well as mouse 3T3 and 10T1/2 cell lines, which are not tumorigenic, were not invasive. In addition, normal primary prostate epithelial cells and benign prostatic hyperplasia cells were not invasive when tested in this assay, whereas malignant prostate carcinoma cells were highly invasive. Parallel experiments with these prostatic cells using the intrasplenic assay for metastasis detection in the nude mouse confirmed the benign behavior of the former cells and the metastatic phenotype of the latter ones. These results suggest that this in vitro test allows the rapid and quantitative assessment of invasiveness and a means to screen for drugs which alter the invasive phenotype of tumor cells.

https://cancerres.aacrjournals.org/content/canres/47/12/3239.full.pdf

A Rapid in Vitro Assay for Quantitating the Invasive Potential of Tumor Cells

A tumor cell line was derived from the fibrosarcoma of a 35-year-old Caucasian man who died without having received chemotherapy or radiotherapy. The in vitro growth properties and transplantability into antithymocytic sera treated mice were characteristic of these malignant cells. An aberrant karyology with marker chromosomes was present. No virus particles were detected. Cancer 33:1027-1033, 1974. ERMANENT CELL LINES FROM ANIMAL TISSUES P were established as early as 1948.23 Most of these were originated from malignant tissues. Although a number of human cell lines have been established in vitro, very few fibrosarcoma cell lines have been described. As far as we are aware, there are reports of approximately eight cell lines derived from osteogenic sarcomas,1,4,Q,10,13,~1 two on rhabdomyosarcoma,12)26 three on liposarcoma,1.9.10 and one each on giant cell sarcomas,l Kaposi's sarcoma,* neurogenic sarcoma,26 synovioma,lO and fibrosarcoma.l The rest of the reported cell lines are all carcinomas. Only a few of these sarcoma cell lines have been fully studied and characterized. In this paper we describe the properties of a tumor cell line (HT1080) derived from a fibrosarcoma of a human male.

Characterization of a newly derived human sarcoma cell line (ht-1080)

Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaques were intravaginally exposed to cell-free simian immunodeficiency virus SIVmac251. We examined formalin-fixed tissues and HLA-DR(+)-enriched cell suspensions to identify the cells containing SIV RNA in the genital tract and draining lymph nodes within the first 24 h of infection. Using SIV-specific fluorescent in situ hybridization combined with immunofluorescent antibody labeling of lineage-specific cell markers, numerous SIV RNA(+) DC were documented in cell suspensions from the vaginal epithelium 18 h after vaginal inoculation. In addition, we determined the minimum time that the SIV inoculum must remain in contact with the genital mucosa for the virus to move from the vaginal lumen into the mucosa. We now show that SIV enters the vaginal mucosa within 60 min of intravaginal exposure, infecting primarily intraepithelial DC and that SIV-infected cells are located in draining lymph nodes within 18 h of intravaginal SIV exposure. The speed with which primate lentiviruses penetrate mucosal surfaces, infect DC, and disseminate to draining lymph nodes poses a serious challenge to HIV vaccine development.

Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells

Two cell lines were derived from an embryonal rhabdomyosarcoma. Cells of both lines grew as monolayers in liquid medium and formed colonies in agar medium. Each line consisted of 2 cytologic types resembling those of the original tumor—spindle cells and large multinucleated cells. No myofibrils could be demonstrated in the cells by light or by electron microscopy nor were virus particles detected. Cells of both lines probably contained myosin-ATPase and cells of line #2 contained myoglobin. Chromosome studies of cell line #1 revealed a stem-line of 51 chromosomes with a consistent karyotype. Three passages of cell line #2 were studied, and no evidence of a stem-line was noted. Chromosome counts ranged from 45 to 170, and consistent marker chromosomes in most cells were present in the form of large metacentrics in the C group.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28196909%2924%3A3%3C520%3A%3AAID-CNCR2820240313%3E3.0.CO%3B2-M

Cultivation in vitro of cells derived from a human rhabdomyosarcoma.

A cell line was derived from an osteosarcoma. Cells grew to high population density in liquid medium and formed colonies in agar medium. The cell line consisted of polygonal or fusiform cells resembling the cells of the original tumor. No collagen fibers or calcium apatite microcrystals could be demonstrated in the cultured cells by electron microscopy nor were virus particles detected. Isoenzyme studies of the cell line revealed the “B” band of glucose-6-phosphate dehydrogenase. Chromosome studies of the cell line revealed a range of stem line number from 58 to 65; chromosome counts ranged from 47 to 183. Some cells had marker chromosome of varied morphology and some had minute chromosomes. Chromosome breaks were found in 30.5% of the cells.

Cultivation in vitro of cells derived from a human osteosarcoma

Abstract A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.

Murray B. Gardner

Papers

Characterization of a newly derived human sarcoma cell line (ht-1080)

Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells

Cultivation in vitro of cells derived from a human rhabdomyosarcoma.

Cultivation in vitro of cells derived from a human osteosarcoma

A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice