Showing papers on "Cancer cell published in 1979"

Establishment and characterization of a human prostatic carcinoma cell line (PC-3).

Abstract: The establishment, characterization, and tumorigenicity of a new epithelial cell line (PC-3) from a human prostatic adenocarcinoma metastatic to bone is reported The cultured cells show anchorage-independent growth in both monolayers and in soft agar suspension and produce subcutaneous tumors in nude mice Culture of the transplanted tumor yielded a human cell line with characteristics identical to those used initially to produce the tumor PC-3 has a greatly reduced dependence upon serum for growth when compared to normal prostatic epithelial cells and does not respond to androgens, glucocorticoids, or epidermal or fibroblast gowth factors Karyotypic analysis by quinacrine banding revealed the cells to be completely aneuploid with a modal chromosome number in the hypotriploid range At least 10 distinctive marker chromosomes were identified The overall karyotype as well as the marker chromosomes are distinct from those of the HeLa cell Electron microscopic studies revealed many features common to neoplastic cells of epithelial origin including numerous microvilli, junctional complexes, abnormal nuclei and nucleoli, abnormal mitochondria, annulate lamellae, and lipoidal bodies Overall, the functional and morphologic characteristics of PC-3 are those of a poorly-differentiated adenocarcinoma These cells should be useful in investigating the biochemical changes in advanced prostatic cancer cells and in assessing their response to chemotherapeutic agents

Role of Superoxide dismutase in cancer: a review.

Abstract: Diminished amounts of manganese-containing superoxide dismutase have been found in all the tumors examined to date. Lowered amounts of the copper-zinc-containing superoxide dismutase have been found in many, but not all, tumors. At the same time, tumors have been shown to produce superoxide radicals. It is shown how diminished enzyme activities along with radical production may lead to many of the observed properties of cancer cells. The apparent exploitation of the differences between normal and cancer cell superoxide dismutase activity in the treatment of cancer is discussed.

Intraperitoneal free cancer cells and their viability in gastric cancer

Abstract: Free cancer cells in the peritoneal cavity of 100 patients with gastric cancer were examined by means of Douglas lavage, and their viability was estimated by 3H-thymidine uptake with autoradiographical technic. Furthermore, the effect of mitomycin-C on the viability of free cancer cells in the peritoneal cavity was studied. The appearance of intraperitoneal free cancer cells was dependent on the degree of invasion of cancer to the gastric serosa; that is, free cancer cells were not found in cases without serosal invasion, but were found in 48% with serosal invasion. The viability of free cancer cells in the peritoneal cavity was relatively high, but could be suppressed remarkably by intraperitoneal administration of 10 mg of mitomycin-C.

Prolactin Receptors in Human Breast Cancer Cells in Long-Term Tissue Culture

Abstract: Prolactin receptors have been identified for the first time in a number of human breast cancer cell lines and a normal human breast cell line maintained in long-term tissue culture. Optimal conditions for determining the binding of 125I-labeled human prolactin to these cells were established. Five different tumor cell lines have different content of prolactin receptors ranging from 2,300 to 26,000 sites/cell. All tumor cell lines contained more prolactin receptors than does one normal breast cell line (1700 sites/cell). The prolactin receptors in these human mammary tumor cells not only bind human prolactin but also recognize other lactogenic hormones such as human growth hormone, human placental lactogen, and sheep prolactin, but not animal growth hormone, which are not lactogenic. The affinity (Ka) of binding of human prolactin to these cells is 4 × 109 m-1 (Kd = 2.5 × 10-10 m). The hormone specificity and affinity for hormone of these human mammary tumor cells are very similar to that found for the rabbit mammary gland. These human mammary tumor cell lines in long-term culture should prove very useful to study the biology of prolactin receptors in living human cells and the role of prolactin in the tumorigenesis of the human breast.

Prolactin Receptors in Human Breast Cancer Cells in Long-Term Tissue Culture1

Abstract: Prolactin receptors have been identified for the first time in a number of human breast cancer cell lines and a normal human breast cell line maintained in long-term tissue culture. Optimal conditions for determining the binding of 125l-labeled human prolactin to these cells were established. Five different tumor cell lines have different content of prolactin receptors ranging from 2,300 to 26,000 sites/cell. All tumor cell lines contained more prolactin receptors than does one normal breast cell line (1700 sites/cell). The prolactin receptors in these human mammary tumor cells not only bind human pro lactin but also recognize other lactogenic hormones such as human growth hormone, human placental lactogen, and sheep prolactin, but not animal growth hormone, which are not lac togenic. The affinity (Ka) of binding of human prolactin to these cells is 4 x 109 ivT1 (Kd = 2.5 x 10~10 M). The hormone specificity and affinity for hormone of these human mammary tumor cells are very similar to that found for the rabbit mammary gland. These human mammary tumor cell lines in long-term culture should prove very useful to study the biology of prolac tin receptors in living human cells and the role of prolactin in the tumorigenesis of the human breast.

Cancer cell estrogen receptor of human mammary carcinoma.

Abstract: Estrogen receptor level expressed as percentages of estrogen receptor-positive cancer cells in the infiltrating cancer cell populations was analyzed with a fluorescent estradiol histochemical technique in fifty-two primary infiltrating and metastatic human mammary carcinomas. The estrogen receptor-positive cancer cells equaled or exceeded the estrogen receptor-negative in number in twelve tumors (23%). The remaining (77%) tumors contained largely estrogen receptor-negative cancer cells. Comparison of the estrogen receptor value in the cytosol derived from tumor tissue homogenates with the histochemical finding in forty cases failed to obtain parallel correlation. Noninvasive intraductal carcinomas were found to be consistently composed of estrogen receptor-negative cancer cells even when present in the vicinity of foci of infiltrating cancer cells with high estrogen receptor activity. In contrast, benign intraductal hyperplastic lesions and papillomas were frequently characterized by piling up of estrogen receptor-positive epithelial cells in the mammary ducts. These observations suggest that when malignant transformation takes place, the cancer cells lose most or all of the progenitors' ability to synthesize estrogen receptors during the intraductal stage of proliferation. This ability is only regained, if ever, by some of the cancer cells during the subsequent infiltrating phase in the stroma. Only occasionally, proliferation of the estrogen receptor-positive cancer cells becomes a prevailing tendency in a human mammary cancer.

Role and regulation of glucose metabolism in proliferating cells.

Abstract: The history of the interest in glucose metabolism in malignantly transformed cells dates back to the pioneering studies of Warburg. These studies led to the statement, in 1956: “The era in which the fermentation of cancer cells, or its importance, could be debated is over and no-one today can doubt that we understand the origin of cancer cells if we know how their large fermentation originates, or to express it more fully, if we know how the damaged respiration and the excessive fermentation of cancer cells originates.” Even at this time, doubts were expressed about the respiratory deficiency of tumor cells.

Direct Inhibition of Growth and Antagonism of Insulin Action by Glucocorticoids in Human Breast Cancer Cells in Culture

Abstract: We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nm). Pharmacological concentrations of dexamethasone (10 nm) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence or absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone. Dexamethasone also inhibited thymidine kinase activity in both control and insulin-stimulated cells. These data suggest multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.

Estradiol formation from testosterone by continuously cultured human breast cancer cells.

Abstract: Two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one cell line derived from normal human breast (HBL-100) were examined for the presence of aromatase activity by determining the amounts of [3H]estradiol ([3(H]E2formed by cell cultures incubated with [3H]testosterone. Aro-matase activity was demonstrable in both breast cancer cell lines, but estradiol synthesis was not observed in HBL-100 cultures. The [3H]E2 content of MCF-7 cultures rose as a function of incubation time and substrate concentration. Furthermore, [3H[E2 formation by this cell line was suppressed by several known inhibitors of human placental aromatase. These observations represent the first evidence that some lines of continuously cultured human breast cancer cells, like some human breast tumors, are capable of forming estrogen from an extracellular precursor steroid. Cultured breast cells may provide model systems for investigating the relative importance of intracellular estrogen formation in the regulation of human breast c...

Trace Elements in Carcinogenesis

Abstract: Carcinogens show extreme diversity in chemical composition and structure. Since they are almost invariably mutagenic, it is generally assumed that they impart, directly or indirectly, genetic damage which results in the genesis of modified viable or nonviable cells. Viable mutant cells are not necessarily malignant. In fact, some authors believe that cancer cells may be associated with specific chromosomal patterns and that each malignant disease is an expression of a specific karyotype. This hypothesis is attractive in view of the existence of neoplastic diseases that are transmitted in a Mendelian pattern and the fact that tumor cells exhibit characteristic morphologies on the basis of which they may be identified. Not all chromosomal changes induced by mutagens or carcinogens are necessarily irreversible. If the initial damage is small and localized, correction through the action of DNA-repairing enzymes is often still possible. Where repair is impossible and viable mutant cell lines are generated, hyperplastic or metaplastic lesions may appear which differ only slightly from the normal cells in the surrounding tissue. Such cell populations may coexist in healthy tissue for extended periods. In organisms with functional immunologic surveillance, “spontaneous” regressions may occur. But if the natural defense mechanisms are weakened, i.e., in old age or after exposure to stress, “carcinoma in situ” or small, avascular, solid tumors eventually appear.

Dynamic aspects of cancer cell populations in metastasis.

Abstract: Consideration of the entire metastatic process reveals it to be very inefficient in terms of cancer cells. Of the millions of cells released from primary cancers, relatively few metastases result. This disparity implies that in some way the process is selective. Some evidence will be reviewed that indicates that cancer cells in metastases are in some way different from those in the primary cancer from which they arose. Primary cancers and their metastases, then, should possibly be regarded as distinct entities when one is considering therapy or seeking an understanding of the fundamental aspects of metastasis. In this presentation some nonexclusive mechanisms will be discussed that could be responsible for differences between primary and secondary cancers. These include: 1) Random (statistical) selection of metastasis-forming cells; 2) The existence of genotypic metastatic subpopulations; 3) The existence of transient metastatic "compartments" within primary cancer; 4) Site-induced changes (modulation) occurring in the metastasizing cells after they arrive in the target organ; 5) A combination of the above.

Junctional Intercellular Communication Pattern of Cultured Human Breast Cancer Cells

Abstract: Junctional intercellular communication between several established human breast cancer cell lines and a variety of mammalian cells has been examined. All the cancer cell lines were found to be either noncommunicators or nonselective communicators. This contrasts with normal human mammary epithelium which shows selectivity in junctional communication. Loss of selectivity in junctional communication appears to be a general feature of cultured human breast cancer cells.

Differences in the Peripheries of Walker Cancer Cells Growing in Different Sites in the Rat

Abstract: Walker 256 cancer cells growing in the ascitic form and following direct injection in the livers and in s.c. sites in rats had significantly higher anodic electrophoretic mobilities than did cells derived from the same source but growing in kidneys and spleens. Following incubation with neuraminidase, the cancer cells from the kidneys and spleen lost significantly less net surface negativity than did cells growing in the other 3 sites. These kidney- and spleen-associated differences were not demonstrably due to preexisting, electrokinetic subpopulations of cancer cells within the original ascites tumor; they were maintained on organ-to-organ passage and were reversed on reconversion of the tumors to ascitic form. The evidence favors site-induced modulation to account for the differences between primary cancers and their metastases are conceivably due to site-induced modulation as distinct from preexisting metastatic subpopulations. Evidence which will be discussed later suggests that the cancer cells in some primary tumors are different from those in their metastases in at least some organs. The nonexclusive possibilities arise of whether these organs were selectively seeded by preexisting subpopulations of cancer cells from within the primary tumor or whether the seeding was random. In either case, the cells in the metastases were different because they were located in specific metastatic sites.

The cytoskeleton in cancer cells in animals and humans.

Abstract: Immunofluorescent staining of human cancer cells with antibodies against actin and myosin shows an important increase of brightness when compared with staining of normal cells from control tissues. Electron microscopic examination of cancer cells shows accumulation of cytoplasmic microfilaments (40--80 A in diameter) with some larger filaments (100--120 A in diameter) scattered in between compared to normal cells from control tissues. Such filaments are particularly abundant at the cell periphery. These findings indicate that the cytoplasmic contractile apparatus of cancer cells is more developed than that of normal cells. Such development may at least in part explain the invasive activity of malignant cells.

Heterogeneous response of disseminated human ovarian cancers to cytostatics in vitro

Abstract: Cell suspensions from nine human ovarian primary cancers, their metastases and ascitic cells were treated in vitro with amethopterin and melphalan. Effects were measured by incorporation of H3-TdR or H3-UdR into the cells. There was significant heterogeneity of cytostatic effects on cells from the three sources in a given patient. Ascitic cells did not represent a “mean” of the cancer cell clones. The implications of these findings should be considered if cytostatic in vitro prediction tests are used to guide cytostatic treatment of patients.

Glycosyltransferase and Glycosidase Activities in Cultured Human Fetal and Colonic Adenocarcinoma Cell Lines

Abstract: Three galactosyltransferases, an N-acetylgalactosaminyltransferase, two sialyltransferases, and glycosidase activities were examined in cultured human colonic fetal and tumor cells and in colonic tumors and adjacent normal mucosa. Although tumor tissues generally had the lowest specific activities of these enzymes, of the four sources examined cultured cancer cells had the highest levels of two galactosyltransferases. A substantial amount of glycosyltransferase activity in cell cultures was secreted into the culture fluid. Differential appearance of glycosyltransferases in the culture media suggests that the media activities are a result not of cell death but of cellular secretion. Thin-layer isoelectric focusing of cell extracts and examination of galactosyltransferase activity revealed differences in isoenzyme profiles among cultured tumor lines. Although most tumor lines had a component with an isoelectric point of pH 4.8, each cell line had a unique complement of galactosyltransferase isoenzymes. The findings that cells secrete large amounts of glycosyltransferases and that tumor cells differ in their galactosyltransferase isoenzyme profiles suggest that the development and chemotherapeutic response of human colonic adenocarcinoma might be followed in an animal model by examination of these enzymes in the sera of nude mouse recipients of these tumor cells or by similar analysis in cancer patients.

Evidence for the Expression of Human Tumor-specific Antigens Associated with β2-Microglobulin in Human Cancer and in Some Colon Adenomas and Benign Breast Lesions

Abstract: The blocking tube leukocyte adherence inhibition (LAI) assay was used to monitor the purification of human tumorspecific antigens (TSA's) from colon and breast cancer and malignant melanoma. The tumor antigens were specific for the organ from which the cancer arose and the histopathology of the cells of origin. Immunochemical studies revealed that TSA could be water solubilized from cancer cell membranes by limited papain digestion, and on Sephadex G-150 chromatography the majority of the TSA eluted in the molecular-weight range of 70,000 to 150,000. Affinity chromatography with anti-human β2-microglobulin (β2m) antiserum indicated that the TSA's, like HLA molecules, contain a β2m subunit. The specificity of binding of the TSA to the anti-β2m immunoadsorbent affinity column and the immunologically specific abrogation of LAI activity were shown. Some patients with either colon adenomas or benign breast disease showed LAI activity to phosphate-buffered saline extracts of colon and breast cancer, respectively, but did not react to extracts of normal colon mucosa or breast tissue. Moreover, the LAI-reactive leukocytes were blocked by the papain-soluble TSA's from colon and breast cancer, respectively, purified by anti-β2m affinity chromatography. The present studies suggest that some “benign” lesions express TSA's before the appearance of morphological evidence of cancer. It is not known, however, if the acquisition of a cell surface TSA is an irreversible step toward unrestrained growth and metastasis. In addition, the present studies indicate that the putative TSA's of cancers of different organs are similar in subunit structure, size, and genetic linkage and have some unexplained relationship to organ definition.

Small cell carcinoma of the lung and its histological origin. Report of a case.

Abstract: A rare lung cancer consisting in part of small cell carcinoma of intermediate cell type and in part of well-differentiated papillotubular adenocarcinoma is described. Alcian blue-PAS staining was observed in the cytoplasm of the small cell carcinoma cells; the Grimelius argyrophil reaction was also positive in the cytoplasm of these cells. Electron microscopy revealed neurosecretory granules in the cytoplasm. At autopsy, a small cell carcinoma of intermediate cell type was found with both squamous features and gland formation. The cellularity and histological pattern of this tumor suggested the existence of a transitional pattern between small cell carcinoma of intermediate cell type, squamous cell carcinoma and adenocarcinoma. From the above findings, we think that small cell carcinoma including the intermediate cell type is derived from respiratory epithelial cells of endodermal origin with dedifferentiation of those cancer cells into neurosecretory cells.

Chromosomes and neoplasia.

Abstract: While it would be satisfying to find that the same cellular process, or even a group of closely related processes, leads to the development of neoplasia, there is no necessity to believe that such a common pathway exists, since cancer includes many diverse diseases, the etiology, biology, clinical presentation, therapy, and prognosis of which will differ very greatly. Our knowledge of cancer cells depends largely on the behavior of the cells in culture and the measurement of various parameters that are not necessarily linked in any causal way with the neoplastic state. From these studies, however, have arisen a number of theories on the nature of neoplasia. For example, it is quite clear that the cell surface of cancer cells is abnormal in many different ways.304 There are new antigenic determinants; there may be altered glycoprotein and sialoprotein structures on the cell surface; the electrical charge and therefore the electrophoretic mobility of the cells may be altered; the absence of some material from the cell surface may also be associated with the acquisition of neoplastic properties (e.g., LETS protein29). Cancer cells also have altered contact relationships with other cells in culture in that they will fail to respond to the presence of other cells and move over or under them, whereas normal cells will usually stop or change direction on coming into contact with other cells.

A Mode of Incipient Growth in Chemically Induced Signet Ring Cell Carcinoma of the Canine Stomach

Abstract: Summary A 31-month-old female mongrel dog was orally administered with 50 mg or 100 mg of N-nitrosobutylurea (NBU) in gelatin-capsule 3 times per week for 19 months with interposing periods of complete suspension.Thirty-four foci of signet ring cell carcinoma were found in the antral region of the stomach.The majority of the foci (31 foci) were early cancer, and the remaining foci were invasive cancer.In addition to these lesions, there was “a single gland cancer” in which a row of cancer cells was confined to a single gland.The whole gland was composed of two cell layers; the inner layer facing the lumen was normal gastric cells and the outer layer was atypical or neoplastic cells underlaid by the basement membrane.Mitosis was frequently observed on the bottom of the gland.Atypical or neoplastic cells seemed to mature gradually through a process of upward migration with increase in cytoplasmic Alcian blue-PAS and HID-AB positive mucin.Some of the cells rich in mucin moved into the lamina propria.The other cells remained in the flow of the regular cell renewal system of the normal gastric cells and reached the top of the gland.This observation revealed a mode of incipient gastric cancer growth, which starts and spreads within a single gland, before it invades the surrounding lamina propria.

Carcinocythemia due to metastatic oat-cell carcinoma of the lung

Abstract: The concept of circulating tumour cells is not new, and several studies have confirmed the presence of these cells by means of various concentration techniques.SA Carey and colleagues5 used the term carcinocythemia to designate the presence in the circulation of carcinoma cells in contradistinction to acute myelogenous leukemia cells, which may complicate chemotherapy6 and radiotherapy7 for primary cancers. They stressed the potential problems and implications of such differentiation. Carey and colleagues interpreted carcinocythemia as carcinoma cell leukemia; however, owing to the conflicting meaning implied by this interpretation, we have chosen to refer to carcinocythemia as the presence in the circulation of carcinoma cells rather than carcinoma cell leukemia. This report describes a case of carcinocythemia in a 48-year-old woman who had primary oat-cell carcinoma of the lung with widespread metastases. The size and features of the cancer cells created initial difficulties in the interpretation of the buffy-coat preparation and the peripheral blood and bone marrow smears.

β-Hexosaminidase Isoenzymes in Tissues, Cultured Cells, and Media from Human Fetal Intestine and Colonic Adenocarcinoma

Abstract: Isoelectric focusing of tissue homogenates revealed a predominance of β-hexosaminidase B in colonic adenocarcinoma, whereas β-hexosaminidase A was greater in paired normal-appearing colonic mucosa from the same patients as well as in a specimen of human fetal colonic mucosa. Because of the recognized cellular heterogeneity of these tissues, our studies were extended to an examination of these isoenzymes in 20 cultured epithelial cell lines derived from human fetal intestine and colonic carcinoma as well as the secreted enzymes in their culture media. While the B:A isoenzyme ratio was higher in human cancer cells as compared to fetal cells, some of the cancer cell lines had a greater proportion of the A isoenzyme. Examination of the isoenzyme profiles in the media of these cells revealed a greater B:A ratio whether of fetal or cancer cell origin. These studies parallel the apparent biological differences of neoplastic colonic epithelium occurring in vivo and are reminiscent of reported oncodevelopmental changes in enzymatic properties present in some malignant tissues. The differential stabilities of these two isoenzymes derived from the culture media of both types of cell lines in vitro may limit their value as markers of human colonic neoplasia.