Showing papers on "Cancer cell published in 1981"

Cholesterol metabolism in cancer cells in monolayer culture. III. Low-density lipoprotein metabolism.

Abstract: The metabolism of low-density lipoprotein (LDL) was studied in neoplastic and non-neoplastic cells of human gynecological origin, in monolayer cultures. The neoplastic cells were derived from epidermoid vaginal carcinoma, epidermoid cervical carcinoma and endometrial adenocarcinoma, in various degrees of differentiation. The non-neoplastic cells were cervical fibroblasts and epithelial cells from proliferative endometrial glands. Both neoplastic and non-neoplastic cells assimilated and degraded LDL in a similar fashion to other human cells (e.g. skin fibroblasts). However, the neoplastic cells metabolized LDL at a higher rate than the non-neoplastic cell (e.g. epidermoid cervical cancer cells metabolized LDL at a 20 times higher rate than did cervical fibroblasts). Such a high rate of LDL metabolism probably enables continuously replicating cancer cells to obtain the large amounts of cholesterol required for cell membrane synthesis. If a high rate of LDL metabolism proves to be a general property of cancer cells, such a property could prove useful for tumor chemotherapy, providing cytotoxic chemicals could be incorporated within the LDL molecule.

The cell cycle.

Abstract: FIFTEEN years ago it seemed that one could selectively damage cancer cells by exploiting simple differences in the cell-cycle kinetics of normal and neoplastic cells Although these hopes have not

Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine

Abstract: The growth in vitro of human breast cancer cells, line MCF-7, was inhibited by a daily supplement of L-arginine (1 milligram per milliliter). Arginine acted synergistically with dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) (10(-6) molar) to enhance the growth inhibitory effect: the cell replication ceased completely within 2 days after treatment. The growth arrest accompanied a change in cell morphology and was preceded by increases in the cellular concentration of cyclic AMP, adenylate cyclase, and type II cyclic AMP-dependent protein kinase activities as well as a decrease of estrogen binding activity. The results suggest that growth of human breast cancer cells is subject to cyclic AMP-mediated regulation and that arginine may play a specific role in this process.

Morphogenesis of Peritoneal Metastasis in Human Gastric Cancer

Abstract: A comparative light microscopic and scanning electron microscopic study of the morphogenesis of peritoneal metastasis in 34 human gastric cancers was performed. Prior to adhesion of gastric cancer cells to the peritoneum, the mesothelial cells became hemispherical and exfoliated from the peritoneum, and gastric cancer cells adhered to the naked areas of the submesothelial connective tissue. A flat metastatic tumor was formed by cancer cell proliferation in the shallow region of the peritoneum. Subsequently, after the infiltration of cancer cells into the connective and adipose tissue, the formation of a large tumor mass was observed. There was a correlation between the surface and histological structure of the metastatic tumors. In poorly differentiated cancer, the cells were isolated while in differentiated cancer, they formed nodules with indistinguishable cell boundaries.

Estradiol stimulates synthesis of a major intracellular protein in a human breast cancer cell line (MCF-7)

Abstract: Previous studies have shown that synthesis of a 24,000 molecular weight (24k) protein (7) and the mRNA activity coding for a 24k protein (8) are selectively stimulated by estradiol in MCF-7 human breast cancer cells. Utilizing a double-label electrophoresis technique to measure the relative rates of specific protein synthesis, the present study relates further characterization of this estrogen response. The 24k protein was found to be stimulated by estradiol provided cells were preincubated with antiestrogen. Under these conditions, antiestrogens inhibit cell growth and addition of estradiol reverses growth inhibition (estrogen growth ‘rescue’). As a control experiment, specific protein synthesis was measured in another growth rescue model produced by withdrawing serum from the medium to inhibit growth and then stimulating cells by readdition of serum (serum growth ‘rescue’). This failed to stimulate synthesis of a 24k protein, implying that the effect observed following estrogen ‘rescue’ was not a non-specific result of growth stimulation. Increased 24k synthesis was found to be both time and estrogen-dose dependent and required specifically those steroid hormones which interact with the estrogen receptor. Moreover, the dose response curve for 24k stimulation paralleled closely the dose response for estrogen stimulation of nuclear estrogen receptor processing, an event correlated with another estrogenic response in MCF-7 cells, induction of progesterone receptor. These findings suggest that estradiol itself directly stimulates synthesis of the 24k protein through interaction with the estrogen receptor system. Further separation of double-label cytosols by two-dimensional electrophoresis resolved the 24k protein into two isoelectric species with pI's in the range of 6.7–6.9 and 6.4–6.7, the latter being the most abundant or rapidly labeling protein. Based on the percentage of total cytosol incorporation contained in individual two-dimensional gel spots, the major species of 24k represented in the fully stimulated cell (3H-counts) about 1.6% of newly synthesized protein. It also represented about 0.7% of newly synthesized protein in the unstimulated (14C-counts) cell, which indicates that 24k is synthesized constitutively. Because of its relative abundance, the 24k protein may be a suitable end product for investigating the mechanisms of estrogen action in human breast cancer.

Required Presence of Both Estrogen and Pituitary Factors for the Growth of Human Breast Cancer Cells in Athymic Nude Mice

Abstract: Estrogen, prolactin, and other pituitary factors are implicated in the etiology of human breast cancer. In the present study, the effects of estrogen and factors from GH3 rat pituitary tumor cells on the growth of T-47D human breast cancer cells were tested in athymic nude mice. Four groups of nude mice were used: Group 1 (T) received s.c. injection of T-47D cells only; Group 2 (TE) mice were given injections of estradiol valerate and T-47D cells; Group 3 mice were given injections of T-47D and GH3 cells (TG), one cell type on each flank; and Group 4 received estradiol valerate and T-47D and GH3 cells (TEG). We found that the human breast cancer cells, T-47D, did not proliferate in Groups 1 and 3 despite the presence of high circulating levels of prolactin and growth hormone produced by the growing GH3 pituitary tumors in Group 3. This suggested that prolactin and growth hormone were not sufficient to stimulate the growth of human breast cancer cells. T-47D cells exhibited only moderate growth in Group 2 but proliferated rapidly in Group 4. The T-47D tumors of Group 4 were 8 times larger than those in Group 2 after 42 days of growth. These results demonstrate that the simultaneous presence of estrogen and pituitary growth factors are required for maximal growth of T-47D human breast cancer cells in nude mice. The identity of the pituitary-dependent growth factor(s) that stimulates the growth in vivo of human breast cancer cells remains to be elucidated.

Malignant potential of murine stromal cells after transplantation of human tumors into nude mice

Abstract: Human malignant cancer tumors grafted into nude mice produce tumors containing both human cancer cells and the host's stromal cells. After short-term propagation of these tumors in vitro, the murine mesenchymal cells appear transformed and are tumorigenic in nude mice. However, established human cancer cell lines fail to similarly after adjacent murine stromal cells when used to produce tumors in nude mice. These experiments suggest that cancer cells may recruit normal cells to become malignant, qualifying the view of the clonal (unicellular) origin of cancer.

Antagonism between Epidermal Growth Factor and Phorbol Ester Tumor Promoters in Human Breast Cancer Cells

Abstract: It has been suggested that the phorbol ester tumor promoters act via the receptor-effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [3H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [3H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation.

Effect of cell density and confluency on cholesterol metabolism in cancer cells in monolayer culture.

Abstract: Cholesterol metabolism in four gynecological cancer cell lines in monolayer culture was evaluated as a function of cell density. The rate of uptake and degradation of [125I]iodinated low-density lipoprotein increased during the first 24 to 48 hr of culture, but decreased thereafter. Once the cells became confluent, the rate of metabolism of [125I]iodinated low-density lipoprotein was only one-tenth that in cells which were in the preconfluent state. The specific activity of 3-hydroxy-3-methylglutaryl coenzyme reductase increased during the first 24 to 48 hr of culture and subsequently declined, reaching a nadir after confluency was attained. The rate of incorporation of [14C]oleate into cholesteryl esters was low when the cells were in the log-exponential phase of replication but increased gradually as cell density increased. The highest specific activity of acylcoenzyme A: cholesterol acyltransferase was attained after the cells became confluent. Generally speaking, there was an inverse relationship between the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the one hand, and the rate of [125I]iodinated low-density lipoprotein metabolism and cholesteryl ester synthesis, on the other. It is concluded that cholesterol metabolism in cancer cells in monolayer culture is regulated, in part, by the rate of cell division. In the cancer cells utilized in this study, it is apparent that cholesterol metabolism was subject to the same regulatory mechanisms as are present in nonneoplastic cells.

Lysosomal cathepsin B-like activity: mobilization in prereplicative and neoplastic epithelial cells

Abstract: Extracellular release of acid thiol proteinase activity by prereplicative and neoplastic epithelial cells was studied in serum-free, chemically defined media (CDM) in vitro. Cells isolated from urinary bladder of male bullfrogs and endometrium of ovariectomized rats each showed preferential secretion of cathepsin B-like (CB) activity within 30 min after exposure to carcinogenic nitrosamines (5 X 10(-4) M) or to mitogenic estrogen 1 X 10(-9) M), respectively. In contrast, release of such proteinase, and stimulation of cell proliferation were far less extensive in rat preputial gland cells treated with estradiol-17 beta. Striking secretion of CB was characteristic of neoplastic, but not noncancerous, epithelial cells from human ectocervix. Neoplastic cells with divergent rates of cell-to-cell aggregation were separated by a filtration method. Those cells with high rates of intercellular aggregation also exhibited higher rates of cell proliferation in CDM, as well as in soft gels, and a greater level of CB release than corresponding cancer cells with a relatively low degree of intercellular adhesion. Brief treatment of neoplastic cervical epithelial cells with liposomes containing entrapped leupeptin, a potent inhibitor of CB activity, elicited a sharp reduction in both cellular thiol proteinase activity and cell growth as compared to appropriate controls. These data indicate that mobilization of lysosomal CB activity in prereplicative and malignant cells may play a significant role in the promotion of cell proliferation.

Morphological and Biochemical Aspects of Adhesiveness and Dissociation of Cancer Cells

Abstract: Publisher Summary The cell surface-associated adhesive factor from tumor cells may play a key role in tumor cell adhesiveness. The factor can be synthesized by well-differentiated tumor cells (characterized by development of junctional complexes) but not by undifferentiated tumor cells. This finding suggests that this adhesive factor may represent an expression of tumor cell differentiation. The emphasis is placed on the hepatoma cells of rat. Its demonstration in embryonic rat liver cells suggests that this adhesive factor might be one of carcinoembryonic proteins; the factor is also associated with the embryonic cell adhesiveness (characterized by development of junctional complexes). The adhesive factor, when characterized, may provide an important model system in the study of the phenomenon associated with gene expression. Any adhesive substance associated with adhesiveness in adult rat liver cells can be separated from the cells, because the cell-to-cell contact is also characterized by development of junctional complexes.

The role of subcellular localization in assessing the cytotoxicity of iodine-125 labeled iododeoxyuridine, iodotamoxifen, and iodoantipyrine

Abstract: There is abundant evidence that Auger effects from125I are singularly damaging if localized within DNA as the thymidine analogue125I-iododeoxyuridine (125IUdR). Recent work with125I-labeled intercalating agents and steroid sex hormones extends these observations by showing cytotoxicity with125I in sites other than the DNA backbone. We have compared the cytotoxicity of125IUdR,125I-iodotamoxifen, a non-steroidal antiestrogen that is translocated from the cytoplasm to the nucleus of receptor containing cells, and125I-iodoantipyrine, a biological indicator of the body water space, in human breast cancer cells (MCF-7) and report that cytotoxicity is critically dependent upon subcellular localization. When clonogenic survival of MCF-7 cells is expressed as a function of the concentration of125IUdR,125ITAM and125IAP in the culture media, the D37 values are 8·10−4, 2.3 and 68 μCi/ml, respectively. However, when survival is expressed as a function of the nucleic acid and protein subcellular fraction,125ITAM is just about as toxic as125IUdR localized within the DNA backbone.

Nuclear Estrogen Receptor Release from Antiestrogen Suppression: Amplified Induction of Progesterone Receptor in MCF-7 Human Breast Cancer Cells

Abstract: This study describes a mechanism by which antiestrogen-suppressed MCF-7 human breast cancer cells in long term culture are rescued by estradiol. In these cells, nafoxidine (1 μM) is a potent inhibitor of cell growth, and unlike estradiol, nafoxidine fails to induce progesterone receptors at any dose tested. If in suppressed cells, nafoxidine-containing medium is replaced by medium containing estradiol (10 nM), cell growth resumes (as measured by increases in total protein and DNA), and progesterone receptor is synthesized. The average rate of progesterone receptor induction in cells treated with estradiol after nafoxidine suppression is 7-fold greater than that of cells which were given estradiol after growth in hormone-free medium. The cells rescued by estradiol from antiestrogen suppression have a 3-fold greater progesterone receptor content at the end of the study than do those cells which received estradiol without nafoxidine pretreatment. The lag period normally seen before progesterone receptor leve...

Prognostic Value of Concanavalin A Reactivity of Primary Human Breast Cancer Cells

Abstract: A prospective, double-blind study was carried out to determine whether activity with concanavalin A (Con A) of human breast cancer cells was related to early disease recurrence. Mammary epithelial cells were isolated from 138 primary human breast cancers. The cells were placed in culture, and their reactivity with Con A was determined with a hemadsorption assay in which human erythrocytes treated with various concentrations of Con A were incubated with the test (mammary epithelial) cells in situ. The Con A half-maximum value was determined as the concentration of Con A at which approximately 50% of the test cells adsorbed erythrocytes. Con A reactivity of the tumors was classified as high or low (half-maximum value less than or equal to 30 or greater than 30 microgram/ml, respectively). Patients were followed for 2 to 60 months after primary surgery (median, 22 months). Those patients having tumors that were highly reactive with Con A were at significantly greater risk of developing early recurrence of their cancers than were those patients with low-reactivity tumors. No correlation was found between Con A reactivity and the age of the patients, their menopausal status, the number of axillary lymph nodes infiltrated with tumor, the number of axillary lymph nodes infiltrated with tumor, the estrogen receptor content of the tumor, or the clinical stage of the disease. These data show that Con A reactivity is an independent discriminator for identifying those breast cancer patients who are at high risk of developing early recurrent disease.

Analysis of aprotinin-induced enhancement of metastasis of Lewis lung tumors in mice.

Abstract: The antiproteinase, aprotinin, has been reported by some workers to inhibit the growth and development of a number of different types of primary cancers in animals; however, its effects on metastasis particularly need clarification. As proteolytic enzymes are thought to be involved in some steps of metastasis, we have investigated the effects of aprotinin on the spontaneous metastasis of Lewis lung (LL) tumors in mice together with its effects on the detachment of cells from primary LL cancers, the development of lung tumors from i.v. injections of LL cells, LL cell adhesion in vitro, and LL cell retention in the lungs. The results suggest that the metastasis-enhancing effect of aprotinin is due partly to promotion of the retention of circulating cancer cells at the vascular endothelium. As these effects could well occur with cancers in general, we conclude that antiproteinases may do more harm than good if used in cancer therapy.

Phospholipid acyl group composition in normal and tumoral nerve cells in culture

Abstract: We have studied the fatty acid composition of total phosphoglycerides from various types of nerve cells in culture. Primary cell cultures were compared with tumoral cell strains. Glial cells exhibited no characteristic pattern when compared to neurons. Tumoral cell phosphogly cerides contained much higher levels of octadecenoic acid and lower levels of C-20 to C-22 polyunsaturated fatty acids than normal cell phosphoglycerides. This observation seems to be a general feature in tumoral cell membranes. It could be of interest in respect to the membrane fluidity of cancer cells.

Glia maturation factor promotes contact inhibition in cancer cells.

Abstract: The effect of bovine glia maturation factor on the growth pattern of cancer cells was investigated in the rat glioma cell line 354A. When the cells were grown in the serum-free defined medium N2 in the absence of the factor, the cells proliferated with a doubling time of 24 hr without showing contact inhibition. After reaching confluency, the cell layer formed numerous foci from which heaps of cell colonies arose. The addition of glia maturation factor to the culture stimulated cell division in the logarithmic phase but prevented overgrowth once the cells arrived at confluency. The ability of glia maturation factor to restore contact inhibition suggests a regulatory role in normal and neoplastic cells.

Cell surface morphology in epithelial malignancy and its precursor lesions.

Abstract: The cell surface organization of cancer cells is of potentially great significance, as it may not only allow (early) diagnosis, but as it may also harbour markers for refined prognosis (degree of oncogenetic and metastatic potential), and targets for selective cancer (chemo- and immuno) therapy. With these aspects in mind, the present review deals with SEM work done on (pre-) malignant cells, both in vivo and in vitro, and in animal models. Attention, however, is focused on human cancer cells. Cancer cells in vitro may lose many of their original malignant characteristics, and show adaptations to culture conditions. Many other factors have been shown to influence cell surface morphology, such as cell cycle, cell contacts, and preparations technique. Cancer cells differ in their surface morphology from normal cells, and have an extra ordinary amount of surface activity. Human malignant epithelial cells show abundant long. pleomorphic microvilli, especially those present in effusions. In squamous epithelium (bladder, cervix) microridge system present on normal superficial cells are progressively replaced by microvilli which increase in number and degree of pleomorphism during experimental and clinical oncogenesis. The question of whether or not the appearance of long. Pleomorphic microvilli reflects an irreversible alteration of the epithelium, and thus provides an early marker of irreversible neoplastic transformation is considered and assessed on the basis of our work with (pre-) malignant cells of the human uterine cervix. Although SEM has contributed significantly to the description of oncogenesis, up to now it has no early diagnostic, prognostic or therapeutic significance.

Comparison of [3H]glucosamine-labeled glycoproteins from human renal cancer and normal kidney epithelial cell cultures by two-dimensional polyacrylamide gel electrophoresis

Abstract: Two-dimensional polyacrylamide gel electrophoresis has been used to compare the Nonidet P-40 soluble, [3H]glucosamine-labeled glycoproteins of human kidney cancer cell lines and short-term cultures of normal kidney epithelia. Two pairs of autologous combinations of tumor and normal cells and also six other cancer lines and four normal cultures were examined. Because autologous cells could be compared, possible differences due to allogeneic variations could be eliminated. The electrophoretic patterns given by tumor and normal cells were extremely similar. Nevertheless, more than 10 differences could be recognized when randomly selected combinations of cancer and normal cells were examined in detail. Of these differences, however, only one was consistently found in all possible combinations of cancer and normal cells. Cancer cells had three prominent components of molecular weight 27,500 and pIs of 5.7, 5.3, and 4.9, respectively. Normal cells have a fainter and different constellation of spots in this region, with the more acid component (pI 4.9) being absent (or barely detectable). The pattern of fetal kidney cells resembled that given by normal adult kidney.