Biological studies of ten human squamous carcinoma cell lines: an overview.

Ten cell lines established from surgical specimens of human squamous carcinomas of the tongue and larynx have been investigated with respect to their motility, ultrastructure, karyotypes, certain biochemical features, interaction with normal epithelial and stromal elements and capacity to infiltrate three-dimensional organoid systems. All the cell lines have maintained several morphological and biochemical characteristics indicating a common origin, although the extent to which each line displays this heritage is variable. The phenotypes of each of the individual cell lines are, however, notably stable.

Interactions between normal epithelial and squamous carcinoma cells in monolayer culture.

Confrontations of rings of adult human oral mucosa epithelial cells enclosing islands of similar normal epithelium, fibroblasts, and cells of three established lines of human squamous carcinoma in monolayer culture were investigated by phase and reflection microscopy and by time lapse cinematography. Measurements of the dimensions of the rings and islands of cells revealed that, while normal epithelial rings confronted with normal epithelium or fibroblasts migrated continuously inwards, similar rings confronting islands of the carcinomas retreated progressively outwards from the tumor islands. The persistence of substantial cell-free space between the epithelium and tumor cells indicated that the outwards migration of the epithelial rings was not solely due to proliferation of the tumor cells.

Five human tumour cell lines derived from a primary squamous carcinoma of the tongue, two subsequent local recurrences and two nodal metastases.

Five tumour cell lines have been derived from a primary squamous carcinoma of the tongue, from 2 subsequent local recurrences, and from 2 lymph-node metastases--all from the same patient. While the cell lines shared many morphological and biochemical characteristics, those derived from recurrences and metastases appeared to be less differentiated, were less well organized in culture, and displayed fewer desmosomes and tonofilaments than cells in the primary tumour line. A recurrent line showing greatest morphological divergence from the primary tumour line also demonstrated the greatest differences at the ultrastructural level, in increased production of plasminogen activator and in the composition of cell-surface glycoproteins.

Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck.

Ten cell lines of human squamous carcinomas of the tongue and larynx have been established from surgical specimens removed from 36 unselected patients, in order to provide systems for investigating the invasive and tissue-destructive capacity of squamous carcinomas of the head and neck. The morphology, ultrastructure and growth characteristics of the 10 lines are described. Detailed cytogenetic analysis of the first 4 lines indicates that each is karyotypically unique, with no evidence of cross-contamination.

Establishment and properties of human germ cell tumors in tissue culture.

Monolayer cultures of nine human testicular germ cell tumors have been attempted, and five have been established as proliferating long-term cultures. All five grew in suspension in nutrient agar, but three proliferated in monolayer culture only when in contact with stromal cells derived from the tumors. Two have been established as "pure" lines, and one of these has been cloned.

Some mechanisms of local bone destruction by squamous carcinomas of the head and neck.

An in vitro osteolysis assay with 45Ca-labelled mouse calvaria has been used to investigate mechanisms of direct bone invasion by squamous carcinomas of the head and neck. Short-term (3-day) organ cultures of 8 fresh squamous carcinomas showed varying degrees of in vitro bone-resorbing activity which was blocked by indomethacin, an inhibitor of prostaglandin synthesis. Supernatant media from 6 established cell lines also induced bone resorption in vitro and evoked an osteoclastic response in the cultured calvaria.

Asymmetrical distribution of epithelial membrane antigen on the plasma membranes of human breast cell lines in culture.

A technique for localizing antigens by immunoperoxidase staining on the surfaces of unfixed culture cells is described. The cells can subsequently be studied by light or electron microscopy. These methods have been used to localize epithelial membrane antigen (EMA) on human mammary carcinoma (MCF7) cells in culture.

Preparation and identification of human breast epithelial cells in culture.

The routine preparation of gram quantities of lobuloalveolar and ductal structures from human reduction mammaplasties by treatment with collagenase is described. When cultured on plastic or glass surfaces these structures give rise, initially, to epithelial sheets consisting of cells which retain many morphological characteristics of myoepithelial cells and do not stain with an antiserum which reacts with the surfaces of the lining epithelium of breast ducts and lobulo-alveoli. Subsequently, cells which resemble the lining epithelial cells migrate from these structures and react strongly with the antiserum.

Polycyclic hydrocarbon activation and metabolism in epithelial cell aggregates prepared from human mammary tissue.

The metabolism of benz(a)anthracene (BA), 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (BP) by human mammary epithelial cell aggregates in culture has been investigated using non-neoplastic tissues obtained from eight patients undergoing reduction mammoplasty. All three hydrocarbons were metabolized to water-soluble and organic solvent-soluble products and the latter included both K-region and non-K-region dihydrodiols. The major dihydrodiols detected as metabolites of the parent hydrocarbons were the 8,9-dihydrodiols of BA and DMBA and the 9,10-dihydrodiol of BP.

Preparation of highly purified cytotrophoblast from human placenta with subsequent modulation to form syncytiotrophoblast in monolayer cultures.

The preparation of highly purified monolayer cultures of human cytotrophoblast cells essentially free of stromal and syncytial cells is described. Such cells subsequently form multinucleate syncytial cells in vitro. This is accompanied by the synthesis of heat-stable alkaline phosphatase and beta-HCG.

An experimental model of cachexia induced by a xenografted human tumor.

A hypernephroma removed from a male patient who had lost 30 kg in weight in the 2 months preceding surgery was established in immunosuppressed CBA/Lac mice as a nonmetastasizing transplantable xenograft. The xenografted tumors, although comprising less than 5% of the total body weight of the mice, produced considerable weight loss (greater than 25%). A slight reduction in food intake of tumor-bearing mice was noted, but some animals bearing mouse or human tumors not inducing cachexia had equally low food intake without accompanying weight losses.

A new experimental model of human cachexia.

A hypernephroma removed from a male patient who had lost 30 kg in weight in the two months preceding surgery was grown as a non-metastasizing transplantable xenograft in immune-suppressed mice. The tumour produced a considerable weight loss (greater than 25 per cent) in the mice at a stage when it comprised less than 5 per cent of the total body weight. A slight fall in food intake of the tumour-bearing mice was noted, but animals bearing other non-cachectic mouse and human tumours had much lower food intakes without accompanying weight loss.

Breast-cancer osteolysis, bone metastases, and anti-osteolytic effect of aspirin.

23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2.

Human breast tumour-induced osteolysis and prostaglandins.

Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate in vitro bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.

The ectopic secretion of calcitonin by lung and breast carcinomas.

Many patients with advanced non-thyroid malignancies have elevated plasma immunoreactive calcitonin concentrations. Breast and bronchial carcinomas contain immunoreactive calcitonin and an epidermoid bronchial carcinoma has been shown to produce immunoreactive calcitonin in vitro. We have established monolayer cultures of breast carcinomas and eight out of fifteen consecutive carcinomas released immunoreactive calcitonin; some released HCG (human chorionic gonadotrophin) or CEA (carcinoembryonic antigen).

Secretion of immunoreactive calcitonin by human breast carcinomas.

Twenty-three out of 28 patients with metastatic breast carcinoma and one out of 13 patients with localised disease had raised levels of plasma immunoreactive calcitonin. Monolayer cultures of breast carcinomas maintained for up to 10 weeks released immunoreactive calcitonin, and a primary breast carcinoma passaged in "nude" mice for over a year contained material immunologically and chromatographically resembling the monomeric form of human calcitonin. These studies indicate that breast carcinomas can produce calcitonin and that plasma calcitonin measurements may be useful in staging patients with breast carcinomas.