Showing papers on "Cancer cell published in 1978"

Direct resorption of bone by human breast cancer cells in vitro

Abstract: OSTEOLYTIC bone metastases occur frequency in patients with advanced malignancy. Breast cancer, the most common malignant disease of women, metastasises to bone more frequently than to any other organ1, and over 80% of patients with advanced breast cancer develop bone metastases2–4. The cellular and molecular mechanisms of bone destruction in patients with cancer are not clearly understood. It has been postulated that there may be two mechanisms, one which is mediated by osteoclasts and one which occurs independently of osteoclasts5,6. We show here that cultured human breast cancer cells have the capacity to resorb directly in vitro, independently of osteoclast stimulation.

Cytochemical study of estrogen receptor in human mammary cancer.

Abstract: A 17beta-estradiol-6-carboxymethyl-oxime-bovine serum albumin--fluorescein isothiocyanate conjugate is prepared by attaching on the average 11 moles of the fluorescein dye and 24 moles of the steroid hormone to each mole of the protein carrier. This fluorescent estradiol conjugate is used as a tracer to detect estrogen receptor of human mammary cancer cells in frozen sections. The cytochemical findings indicate that mammary carcinomas are composed of heterogeneous populations of receptor-positive and receptor-negative cancer cells in varying proportions and probably should be classified according to the percentages of receptor-positive cells in the cancer cell populations for better correlation with endocrine therapies.

Increased CTP synthetase activity in cancer cells.

Abstract: AN insight into the biochemical strategy of cancer cells has been achieved by the conceptual and experimental approach provided by the molecular correlation concept1,2. Studies carried out using this approach with model systems of rat hepatomas and kidney tumours of different growth rates revealed a biochemical imbalance in cancer cells, which manifested itself in progressive changes in activities of key enzymes and overall metabolic pathways that correlated with tumour growth rate1,2. Some of these biochemical alterations have been shown to apply to human primary liver3 and kidney4 carcinomas. Those alterations in gene expression that are linked to the increase in the expression of malignancy are manifested in the increased activities of key glycolytic-, purine-, pyrimidine-, DNA- and polyamine-synthesising enzymes1–8. Concurrently, decreases occur in the activities of the key enzymes of gluconeogenesis, purine and pyrimidine catabolism and of the urea cycle1–5,9,10. In addition to such a progression-linked (growth-rate-linked) metabolic imbalance, the reprogramming of gene expression in cancer cells entails transformation-linked alterations that are present in all hepatomas irrespective of growth rate or extent of differentiation1,2,11–15.Here we report that CTP synthetase (UTP:L-glutamine amido ligase, EC 6.3.4.2) increased in all the hepatomas examined, the activity being highest in the rapidly growing tumours. Thus, in liver neoplasia the activity of this enzyme is both transformation- and progression-linked. CTP synthetase activity was also markedly increased in transplantable kidney tumours in the rat and in primary renal cell carcinomas in man.

Cytological and functional analysis of inflammatory infiltrates in human malignant tumors II. Functional investigations of the infiltrating inflammatory cells

Abstract: Six individual human carcinomas displaying an unusually strong inflammatory reaction were dispersed by a mixture of collagenase and deoxyribonuclease and fractionated in 1 × g velocity sedimentation. This method gave an excellent separation of cancer cells from infiltrating inflammatory cells. The viability in both cell populations exceeded 95%. Blood mononuclear leukocytes and tumor-infiltrating inflammatory cells from the cancer-bearing patients were then tested in the short-term 51Cr release test for in vitro cytotoxicity to their autochtonous tumor cells and to target cells known to be sensitive to the socalled “natural killer” (NK) lytic effects. In two patients with testicular seminoma, the blood leukocytes were strongly cytotoxic to the patients' own tumor cells; in one case of thyroid carcinoma, the patient's blood leukocytes also exhibited a distinct albeit slight cytotoxic activity towards his autochtonous tumor. Blood mononuclear leukocytes of all these cancer patients were strongly cytotoxic to the NK targets MOLT-4, K-562, chicken red cells and human embryonic fibroblasts (Ef). In striking contrast, the tumor-infiltrating inflammatory cells were entirely unable to lyse the autologous tumor cells. Neither, with the exception of the Ef targets, did the tumor-infiltrating cells display any cytotoxic activity towards the NK targets. The findings demonstrate a widespread functional paralysis (or absence) of effector cells directed to the patients' own autologous tumor cells and to NK target cells in the tumor-infiltrating inflammatory cell population.

5-Thio-D-glucose selectively potentiates hyperthermic killing of hypoxic tumor cells

Abstract: To investigate the mechanisms by which heat affects cancer cells, we used 5-thio-D-glucose, an inhibitor of glycolysis in HeLa S-3 cells, under aerobic and hypoxic conditions at temperatures ranging from 37 degrees to 43 degrees C. Drug alone or heat alone killed a minimum number of cells under aerobic or hypoxic conditions. Exposure to drug and hyperthermia selectively increased the number of cells killed under hypoxic conditions at temperatures as low as 40.5 degrees C but had little effect on cells incubated under aerobic conditions. These results suggest that the glycolytic pathways is a primary site of hyperthermic damage leading to cell death.

Lactate dehydrogenase in estrogen-responsive human breast cancer cells.

Abstract: Lactate dehydrogenase activity (LDH) was measured in the MCF-7 human breast cancer cell line derived at the Michigan Cancer Foundation from a patient with metastatic breast adenocarcinoma. LDH was found in the 46,000 X g supernatant of cell lysates, but not in the culture medium. Only the fifth isozyme (LDH-5) could be demonstrated by cellulose acetate electrophoresis and relative heat inactivation studies. When endogenous steroids were removed from the medium, addition of estrogen to the growth medium for several days elevated LDH 2-fold above controls; LDH was not altered when MCF-7 cells were treated with progesterone, hydrocortisone, prolactin, insulin, or triiodothyronine. A physiological concentration (0.1 nM) of 17beta-estradiol was sufficient to produce a maximal LDH increase. There were no qualitative isozyme changes in response to estrogen. LDH activity may therefore be a useful marker protein for studying hormone action in the MCF-7 human breast cancer cell line.

Some mechanisms involved in cancer cell detachment by necrotic material

Abstract: Factors influencing cell detachment are thought to play a role in metastasis and invasion. Previous studies on cylinders punched from Walker 256 (W-256) tumors growing in rats showed that detachment of viable cancer cells was facilitated by their proximity to necrotic regions and exposure to a necrotic extract. By the use of pure cultures of W-256 cells, it is shown that necrotic extracts which are rich in lysosomal hydrolases act directly on W-256 cells, facilitating their in vitro detachment. Lysosomal enzymes have previously been shown to facilitate cell detachment. The partial inhibition of this process by hydrocortisone suggests that the extracts also act by labilizing the W-256 cell lysosomes; this enzyme release is also demonstrable by direct assay. Although secondary lysosomes could not be visualized in the W-256 cells, both they and macrophages release lysosomal hydrolases on freeze-thawing, and could both account for the high enzyme content of the necrotic regions, by a process of continuous secretion and/or cell input. Histologic examination of perinecrotic and peripheral regions of tumors showed a higher proportion of macrophages in the former, which is thought to be mainly due to differential trapping of the macrophages. The results emphasize the functional properties of necrotic regions of tumors and the necessity of referring to specific regions of the same tumor when referring to its metastatic and other properties.

Rat macrophage-mediated toxicity to cancer cells; effect of endotoxins and endotoxin inhibitors contained in culture media.

Abstract: The cytotoxic effect of normal or BCG-activated rat macrophages on a syngeneic line of cancer cells was compared in media containing rat or bovine sera. Normal macrophages were usually cytotoxic to cancer cells in fetal or newborn bovine serum; however, they enhanced cancer cell growth in normal rat serum. BCG- activated macrophages were toxic to cancer cells regardless of the serum used in the assay. Many cell culture media or sera obtained commercially were found to be contaminated by bacterial endotoxins. When endotoxin-free reagents were used in the toxicity assay, different results were observed: normal macrophages were not cytotoxic, but rather, they often enhanced cell growth even in fetal bovine serum; toxicity of activated macrophages was significantly reduced in normal rat serum. These results suggest that endotoxin and endotoxin inhibitors play a role in the modulation of macrophage-mediated cytotoxicity. These results emphasize the importance of monitoring endotoxin contamination in cell culture reagents used in assays involving macrophages.

Antiproliferative Agents and Differential Survival between Normal and Cancer Cells

Abstract: A basic difference in response between normal cells (primate fibroblasts) and colonic cancer cells (human and rodent) to the antiproliferative action of both N-(phosphonacetyl)-L-aspartate and thymidine is described in this report. Both normal and colonic cancer cells, when cultured in the presence of these agents, cease to increase their cell numbers. Evidence is presented to show that the normal cells respond to deprivation of pyrimidine nucleotide induced by these agents by simple growth arrest, in which a quiescent state may be maintained for prolonged periods without cell death. Cancer cells are shown to respond in a characteristically different manner in which cell division continues accompanied by limited cell survival, with the surviving population representing a balance of these opposing processes. The extent to which these in vitro findings, based on a limited number of comparisons under restrictive artificial conditions, relate to the in vivo state remains to be established.

In vivo and in vitro lysis of mouse cancer cells by antimetastatic effectors in normal plasma.

Abstract: Results of parallel in vivo (IV. challenge) and in vitro (trypan blue staining) tests suggest that normal molecular factors in mouse blood can rapidly lyse malignant cells that enter the circulation. An inverse relationship was seen between the ability of malignant cells to form metastases after IV. injection and their susceptibility to lysis in vivo and in vitro. A mammary carcinoma lost its susceptibility to lysis and gained an ability to form metastases with conversion to the ascites form. The factor(s) active against tumor cells in vitro was were most evident in whole plasma, less so in serum form. The factors active against tumor cells in vitro globulin fraction of normal serum. Whole serum from tumor hosts had lower activity than whole normal serum, but had gained some activity in the immunoglobulin fraction. Treatment of normal animals with immunogens reduced the antitumor activity of whole serum. Whole-body irradiation, and, to a lesser degree, cyclophosphamide treatment, increased the activity.

Antigen shedding by human breast-cancer cells in vitro and in vivo.

Abstract: Human breast cancer cells were adapted to chemically defined medium in order to recover naturally shed glycoproteins. Sephadex G-150 chromatography of these glycoproteins revealed 1 major and 2 minor peaks. When the cells were grown in the presence of 3H-leucine, the radioactive shed proteins had a Sephadex profile identical to the unlabelled shed glycoproteins. PAGE analysis of these proteins showed 5 major bands. Antigenically similar proteins were found in the serum of female nude mice bearing BOT-2 tumours, but not in controls.

Separation of lymphoid cells with a suppressor effect on the activity of cytotoxic cells in vitro during the growth of a syngeneic mouse tumour.

Abstract: One or 4 weeks after grafting of a syngeneic sarcoma (T2) to C57BL/6 mice, lymph-node cells (LNC) are cytotoxic in vitro for the cells of this tumour. But after 2 weeks LNC are not cytotoxic or show a non-significant activity. These second-week LNC, added to cytotoxic lymphocytes (CL) from the first or fourth week, reduce considerably the cytotoxicity of the latter cells. When velocity sedimentation at unit gravity is used to fractionate 11th-14th day LNC, some fractions, enriched in small lympoid cells, kill the cancer cells. Other fractions, containing large blast cells, lack this property but can suppress the activity of the small cells or of fourth week CL. These suppressor cells can also be separated from active CL by passage on a glass bead column. They are "adherent" while CL are non-adherent at this stage. This suppressor effect is abolished when the lymphoid cell suspension is treated by anti-theta serum, but macrophage depletion does not modify the inhibition. The cell responsible for the suppressor effect is thus a large T lymphoid cell, adherent and non-phagocytic. It seems to act essentially on an effector phase of the cell-mediated cytotoxicity.

Relation between Steroid Receptor Content and the Response to Hormone Addition in Isolated Human Breast Cancer Cells in Short-Term Culture

Abstract: The hormone dependence of human breast tumors has been investigated in two ways: ( a ) estradiol and progesterone receptor determination in tumor tissue; and ( b ) measurement of the growth-stimulating effect of hormones on cells in short-term culture. Preliminary results from 15 tumors suggest that such a model may be used for human breast tumors. The behavior of the cultures under hormonal stimulation depended on their receptor content. In this series of patients, the tumors containing both estradiol and progesterone receptors were stimulated by addition of insulin and estradiol while the tumors containing either estradiol receptor alone or no steroid receptor were not modified by hormonal addition.

Estrogen Action following Irradiation of Human Breast Cancer Cells

Abstract: Estrogen responsiveness of human breast cancer cells after radiotherapy was examined with the use of the MCF-7 breast cancer cell line (derived at the Michigan Cancer Foundation from a aetastatic human breast adenocarcinoma). Estrogen receptor binding characteristics were unaltered in MCF-7 cells, which survived highly destructive doses of γ-radiation. Biological responses to estrogen were also normal in surviving postirradiated cells. Initial experiments demonstrated that cytosol preparations from MCF-7 cells could be directly irradiated with 20,000 rads of Co 60 γ-rays (single dose) without any net alterations of the binding capacity of estrogen receptor for ligand. Subsequent studies with the use of postirradiated whole cells showed that MCF-7 cell proliferation was inhibited in a radiation dose-dependent fashion. A small percentage of the cell population survived nearlethal doses of radiation. Cells surviving a single dose of 1000 rads were grown to confluence, subcultured, and studied further; they were designated MCF-7R. Both the binding affinity and capacity of MCF-7R cytosol and nuclear estrogen receptors were unchanged from nonirradiated cells. The population doubling time of MCF-7R cells was 43 hr even after 4 months of culture, whereas that of MCF-7 control cells was still 34 hr. MCF-7R cells treated with 10 nm 17β-estradiol responded normally with a 2-fold elevation in lactic dehydrogenase activity compared to untreated controls. Furthermore, inhibition of MCF-7R cell growth by the antiestrogen nafoxidine could be rescued rapidly by subsequent treatment with estrogen. These experiments provide evidence at the cellular level that irradiated tissues can be used for receptor assays and that breast cancer patients may still be amenable to endocrine therapy of recurrent and/or metastatic lesions following extensive local radiation therapy.

HPC-36: an epithelial tissue culture line derived from human prostate adenocarcinoma.

Abstract: The development of a tissue culture line of human prostate adenocarcinoma has been described. The culture (HPC-36), derived from tumor tissue explants, is purely epithelial, with characteristics of neoplastic cells. These include a large nuclear size relative to the amount of cytoplasm, multiple nucleoli within the nucleus, many mitotic figures, the formation of multinucleated giant cells, and loss of contact inhibition. The cells also stained positively for acid phosphatase and have been grown in monolayer and suspension cultures. The HPC-36 cells are presently being studied to determine whether they are true descendants of the cancer cells.

Immunohistological Studies of CEA, AFP and CPALP in Gastric Cancer

Abstract: In studying 150 cases of gastric cancer, 93 (62%) were found to be CEA-positive. Among them, 5 cases had concurrent elevation of serum AFP over 200 ng/ml and appearance of serum CPALP. Further, there were another 2 cases simultaneously positive in serum CPALP. All these 7 cases were of pathologically well-differentiated adenocarcinoma with liver metastases. Immunohistologically, CEA was observed on the surface of cancer cells as well as in glandular lumens of cancer tissues, forming a centroglandular pattern, while CPALP was detected in cytoplasm of cancer cells generally but absent in glandular lumens, and no formation of centroglandular pattern was observed. In contrast, most of the cancer cells were found AFP-negative except for some cancer cells with abundant chromatin in nucleus and acidophilic cytoplasm, in which AFP was detected in cytoplasm. Furthermore, AFP was also scarcely observed in cytoplasm of some normal liver transient cells scattered close to metastatic cancer lesions, suggesting that in gastric cancer, occurrences of CEA, AFP and CPALP originate from cancer cells while mild amounts of AFP are also being synthesized in some normal liver transient cells scattered close to metastatic cancer lesions.

Protein kinase activities in X-radiation-induced adenocarcinoma of rat small bowel.

Abstract: The activities of cyclic adenosine-3',5'-monophosphate (cAMP)-dependent and -independent protein kinases were measured in cellular homogenates prepared from an x-radiation-induced mucoid adenocarcinoma of Holtzman rat small bowel Comparisons of these activities were made with those observed in similar cell preparations of normal unirradiated small bowel tissues and those irradiated intestines which did not have visible lesions A significantly lower degree of cAMP-dependent endogenous and exogenous protein (histone) phosphorylation was observed in the cancer cells compared to that in other tissues In addition, the activities of enzymes in tumor tissue appeared independent of the homogenate concentrations and were not stimulated by cAMP The results suggest that either the radiation-induced cancer consists of cells which no longer respond normally to extracellular signals that are transmitted intracellularly by the cAMP system or a more rapid phosphoprotein phosphatase(s) exists in these cells which may be reversing the process of protein phosphorylation

Establishment and characterization of a new human urinary bladder carcinoma cell line (PS-1).

Abstract: An epithelioid cell line (PS-1) has been established from a transitional cell cancer derived from human urinary bladder. Subcutaneous injection of the epithelioid cells into weanling athymic nude mice induced solid tumors histologically similar to the original tumor. A cell line was also established from a tumor induced in the athymic nude mouse (PS-1, T-1). Both cell lines exhibited essentially identical growth characteristics and formed a monolayer growth of epithelioid cells in culture. Electron microscopic studies confirmed epithelioid morphology. No fibroblastoid elements were observed. Chromosomal analysis revealed heteroploidy with persistent marker chromosomes; all cells contained a Y chromosome. The presence of tumor-specific antigen(s) in PS-1 cells was suggested by microcytotoxicity assays with peripheral allogeneic lymphocytes from other transitional cancer cell patients. Sera of urinary bladder cancer patients reacted with nuclear antigens of the established cells.

The Nature of the Immune Response

Abstract: This chapter discusses the nature of the immune response. One of the most exciting fields of modern immunology is the recent evidence of the role of immunological processes in controlling cancer. It appears that the body recognizes cancer cells as foreign. In this way, an immunological reaction starts in an attempt to control the growth and spread of the malignant cells. In most cases of clinical cancer a fine balance is set up with the scales weighted slightly in favor of the malignant cells so that the cancer progresses but in a slow and sure manner. It is suspected that the malignant clones of cells are produced continuously throughout life but are eliminated rapidly by the body's immune processes. It is only in those cases where the immune response is in some way slightly deficient that the cancer can spread throughout the body. A new approach is being made for the treatment of cancer by attempting to develop means by which it might be possible to enhance the immunological response of the body against cancer and tip the fine balance between the immune reaction and the malignant cells in a more favorable direction.

The Immunology of Cancer

Abstract: This chapter discusses the role of immunological processes in the control and development of cancer It describes the changes occurring in the cancer cell, which makes it different from other cells Cancer cells do not appear to be recognized immunologically by the body completely as part of self The tumor cells loses some of the normal tissue specific antigens, and appears to gain new tumor specific antigens that are not previously present in the cells from which they are derived The loss of normal tissue specific antigens appears to be associated with the functional differentiation that is associated with the neoplastic changes that occur within the cell The cancer cell becomes biochemically different from the tissue from which it is derived The chapter discusses the inborn defense mechanisms of the body against the uncontrolled proliferation of such cells Once a tumor has already developed in the body, it develops a state of equilibrium with the immunological defense mechanisms directed against it This state of equilibrium can be considered to be favorable to the tumor, or otherwise it would be eliminated completely

[Electron-microscopic histochemistry of phosphohydrolases in the normal mucosa and in the cells of human gastric adenocarcinoma].

Abstract: Electron-histochemical study of phosphohydrolases (ATPase, acid and alkaline phosphatases) in cells of the normal gastric mucosa, duodenal mucosa and gastric adenocarcinoma of man was carried out. In cancer cells retaining to a certain extent the ultrastructural features of the chief cells, parietal cells of enterocytes, the distribution of the product of reaction for ATPase and acid phosphatase in nucleoli, endoplasmic reticulum membranes, intracellular cannaliculi, plasmalemma, mitochondria, the distribution of the product of reaction for ATPase and acid phosphatase in nucleoli, tural features of enterocytes, no activity of alkaline phosphatase could be demonstrated in membranes of the villi of the striated border. Alongside with the retention or disappearance of electron-histochemical features, some of them may be enhanced. Thus, the activity of acid phosphatase was increased in lysosomes of cancer cells (of the type of chief cells). So, in cancer cells of adenocarcinoma the structure-functional rearrangement going in different directions is observed in addition to the process of simplification and unification.

The retention of circulating Walker-256 cells by Walker-256 tumours.

Abstract: When Walker-256 cancer cells are injected into the portal veins of rats bearing Walker-256 tumours in their livers, the retention of the injected cancer cells by the tumours is considerably less than in the surrounding liver. After applying defined general criteria for "homing" phenomena to the data, it is concluded that compared with the liver, they demonstrate "antihoming". The observations are explained in terms of a deficient arrest process within the tumours.

Ultrastructural characteristics of renal cancer cells

Abstract: The ultrastructural study of the renal carcinoma revealed some differences in the fine structure of the two main cell types: clear and dark cells. The cytoplasm of clear cells is rich in fat and glycogen. Fat is found in lipid vacuoles and glycogen in diffuse granularity in the cell cytoplasm. Dark cells contain small amounts of fat and glycogen but have well developed mitochondria and other organelles. Comparison of these cell types shows some features of their similarity such as microvilli on the cell surface, desmosomes and interdigitations in the region of cell contacts and channels between tumour cells. These features suggest that clear and dark cells have a common origin from the epithelium of the proximal tubules.