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S Matzku

Publications and source records attributed to S Matzku.

At least 73 records · Page 4Linked to original sources
PubMed1984

Natural cytotoxicity in lymphatic metastasis. I. In vitro studies using the rat tumor BSp73 and its variants.

Serial transplantation of primary BSp73 ascites cells to a subcutaneous (SC) site gave rise to the appearance of two solid variants differing in their capacity to metastasize via the lymphatics. Tissue cultures derived from variant AS (nonmetastasizing) showed epithelioid morphology, while cultures derived from variant ASML (metastatic) showed spherical morphology. Upon cloning, both variants proved to be operationally homogeneous. Susceptibility of cultured BSp73 cells to NK and macrophage-mediated cytotoxicity was closely correlated to morphology, inasmuch as epithelioid cells were susceptible, while spherical cells were resistant, to lysis. With stimulated effector cells a general increase in cytotoxicity was observed, but epithelioid cells still showed a higher susceptibility level. Resistance of ASML-type cells to natural cytotoxicity was not due to the lack of recognition structures or to a general increase in the mechanical stability of spherical cells. This was concluded from cold target inhibition and from hypotonic shock treatment experiments, respectively.

Animals↗
PubMed1984

Natural cytotoxicity in lymphatic metastasis. II. In vivo studies with BSp73 variants differing in metastatic capacity.

The survival of cloned variants of the BSp73 tumor differing in susceptibility to natural killer (NK) and macrophage-mediated cytotoxicity in vitro was evaluated in syngeneic animals. The cytocidal effect was assayed by whole-body determination of (125I)5-iodo-2'-deoxyuridine (125IUdR) retention in intact animals and in animals depleted of phagocytes and/or radiation-sensitive lymphocytes. The following results were obtained: (1) In the peritoneal cavity, survival of the susceptible tumor cells (variant AS) was significantly higher in rats pretreated with radiation and silica than in untreated rats. (2) Cold target competition, response modification by C. parvum, and correlation of label excretion with survival of animals supported the notion that excretion rates of radioactivity were in fact determined by natural cytotoxicity in vivo. (3) Tumor cells resistant to natural cytotoxicity in vitro (variant ASML) were nevertheless killed in vivo (IP) by NK cells and macrophages. (4) Additional elements of tumor cell destruction were active upon IV injection of both AS- and ASML-derived cells, since rapid label excretion was observed irrespective of irradiation and silica treatment or addition of excess unlabeled competitor cells. The apparent increase in susceptibility of ASML cells in vivo might be due to a shift in phenotype induced by microenvironmental factors. No evidence was gained that differences in metastatic capacity exhibited by the variants might relate to differential action of natural cytotoxicity on these cells.

Animals↗
PubMed1984

Cathepsin B-like proteinase as a marker for metastatic tumor cell variants.

Serial transplantation of a spontaneous BDX rat tumor, classified as an anaplastic sarcoma, gives rise to two variants; a rapidly growing nonmetastatic line (AS) and a slowly growing, invasive, and highly metastatic variant (ASML). The availability of two cell lines of the same origin but with markedly differing metastatic potential offers an ideal model for the identification of the cellular properties involved in invasive and/or metastatic behavior. The present work focuses on the pattern of various proteinases in the two tumor cell variants. The findings disclosed one major consistent difference which relates to a cathepsin B-like cysteine proteinase. The metastatic ASML variant manifests exceedingly high intracellular cathepsin B-like activity; in the nonmetastatic AS variant, the activity of this proteinase is significantly lower. Other proteinases, in particular elastase-like, chymotrypsin-like, collagenase-like enzymes and plasminogen activator, showed low, essentially comparable activity patterns. Thus, cathepsin B-like proteinase is a marker enzyme of the metastatic ASML tumor cell variant.

Animals↗
PubMed1983

Natural killer (NK) cells in the rat: "heterogeneity" as reflection of the activation status.

Rat natural killer (NK)/natural cytotoxic (NC) cell activity was tested in a 4-h and a 20-h 51-Cr-release assay. In the 4-h assay, NK activity was high with peritoneal cells (PC), medium with peripheral blood lymphocytes (PBL) and spleen cells and low with bone marrow (BM), thymus and lymph node (LN) cells. The differences in lytic capacity were less pronounced in a 20-h assay. This led to the suggestion that NK/NC cells may get activated upon coculture with tumor cells during the long-term assay and that the short-term assay actually reflects the activation status of NK/NC cells in different organs rather than non-identity of cells with natural cytotoxic potential. This was supported by the following observations: 1. After in-vivo or in-vitro activation of NK cells, increased reactivity was observed in a 4-h assay especially with lymphoid cells of organs with low or medium NK activity and the differences to a priori highly active organs were significantly diminished. 2. Neither by biophysical (density) nor by biochemical (surface markers) methods differences between NK versus NC cells could be substantiated. 3. Closely related patterns of cytotoxicity were observed using adherently growing or lymphoid tumor target cells.

Animals↗
PubMed1983

Solid tumor-derived target cell susceptibility to macrophages and natural killer/natural cytotoxic cells in the rat.

Cytotoxic capacity of rat macrophages (M phi) and natural killer (NK)/natural cytotoxic cells (NC) against adherent growing, solid tumor-derived target cells was evaluated, modulating the activation status of effector cells and growth conditions of target cells. Testing a panel of target cells, cytotoxicity of NK/NC and M phi was strikingly correlated so that besides of target-cell binding structures basic lysability seems to be of influence with respect to cytotoxicity rates. Varying the in vivo growth conditions of target cells altered their lysability by M phi and NK/NC cells in the sense that ascitic versus subcutaneously (sc) grown tumors were more resistant to lysis. On the other hand, in vitro culturing did not influence susceptibility for M phi, but with some tumor lines increased lysis by NK/NC cells was observed. In the rat, the activation status of M phi and NC was not age-dependent, and NK cell activity only declined slowly with age. But cytotoxic potential of M phi obviously presents a strain characteristic, different from NK/NC cell activity, only the latter two correlating in different rat strains. Experiments to augment natural cytotoxic capacity revealed that application of Corynebacterium parvum (CP) activated M phi and NK/NC cells, while sc tumor implantation only resulted in increased NK/NC cell cytotoxicity, leaving M phi unaltered.

Animals↗
PubMed1983

Rat natural killer (NK) cells are not bone marrow dependent.

Rats were treated with various doses of 89Strontium. At a dose effecting depletion of the bone marrow (200 muCi), NK activity of spleen, peritoneal and peripheral blood lymphocytes was unaltered or only slightly decreased. At higher doses (400 muCi), a general impairment of the immune system, including T-cell functions, was observed. After application of 700 muCi 89Strontium, rats died within three weeks.

Animals↗
PubMed1983

DNase I inhibitions in tumors of different metastasizing capacities: a possible index of invasiveness.

Tumor pairs, selected on the basis of their different capacities to metastasize in vivo (SP73/AS and ASML from the rat, Eb/ESb from the mouse), have been assayed for their membrane associated actin through the DNase inhibition assay. It is found that, provided inhibitions per cell are corrected for the influence of gross heterogeneities in size distributions, the more metastatic tumor cells have significantly higher DNase I inhibitions than their less invasive counterparts. This observation, which extends our previous study of normal recirculating lymphocytes, is rationalized by postulating a participation of these actin pools to a property critical for both normal recirculation and metastatic spreading, arguments are presented which favor cell surface deformability as a possible candidate.

Actins↗
PubMed1983

Postsurgical follow-up of colorectal cancer patients monitored by the leukocyte migration test.

Blood samples from more than 1,000 patients with colorectal cancer were tested in the leukocyte migration test (LMT) and by a radioimmunoassay for carcinoembryonic antigen (CEA) for evaluation of: 1) the correlation of LMT response to the status of disease and 2) the use of LMT and CEA determination in the monitoring of patients after surgical removal of the primary tumor. A total of 320 patients, which were tested repeatedly, constituted the key group of the investigation: Of these, 56 patients developed recurrences or metastases whereas 217 patients showed no sign of reactivated disease. The group of patients with persistent absence of disease showed test profiles of either persistent negativity (50%) or conversion of one or both parameters; persistently positive profiles were rarely encountered. Patients with recurrences and metastases showed either positive profiles or conversion of positivity; only 3 patients were negative in both tests. However, despite significant disease-related response of the LMT, the test is not recommended as an adjunct to postsurgical monitoring, because of its technical complexity.

Carcinoembryonic Antigen↗
PubMed1983

Characterization of BSp73, a spontaneous rat tumor and its in vivo selected variants showing different metastasizing capacities.

BSp73 arose spontaneously (1979) as intraperitoneal nodules together with ascites. Histologically, the nodules were classified as adenocarcinoma of the pancreas. During serial transplantation of ascites cells to a subcutaneous site, two variants appeared--one fast-growing, nonmetastasizing, the other slowly growing and metastasizing via the lymphatic system to the lung. From the in vivo selected variants as well as from the parental tumor, two types of tissue cultured cell lines were established. These differed in morphology, adherence to plastic, susceptibility to detachment by trypsin, and, above all, in the ability to metastasize upon reinjection into syngeneic recipients. From differences in growth kinetics in vivo it has to be concluded that variant cell types coexisted in the parental tumor in the form of precursors, which adopted their characteristic features (irreversibly) after a shift in the environment.

Animals↗
PubMed1982

Mechanisms of cellular cytotoxicity mediated by effector cells from rats with spontaneous tumors.

We have previously shown that effector cells from BD X rats bearing spontaneous tumors display increased cytotoxicity towards syngeneic tumor cells compared to effector cells from untreated rats (Zöller and Matzku, 1980 a). The increased in vitro cytotoxicity of lymphoid cells from tumor-bearing (TB) animals was not T-cell mediated and the question was raised, whether it was due solely to increased natural killer (NK) cell activity, or whether humoral factors could also be involved. We now prove that in a long-term assay, the presence of B cells is indeed mainly responsible for increased TB cytotoxicity, since: (1) After depletion of surface immunoglobulin positive cells (s-Ig+), TB cytotoxicity no longer exceeds cytotoxicity of effector cells from untreated rats; (2) Mixtures of s-Ig+ cells from TB animals with Fc-receptor positive (Fc-R+) cells from untreated rats restore the increased TB cytotoxicity; (3) Addition of rabbit Fab' anti rat F(ab')2 reduces TB-effector cell cytoxicity. A minor contribution of the increased TB cytotoxicity by activation/numerical increase of NK cells will be discussed.

Animals↗
PubMed1982

Rat macrophages inhibit natural killer (NK) cell activity against adherent growing target cells.

Peritoneal as well as peripheral blood, but not spleen macrophages inhibit natural killer (NK) cell activity directed against adherent growing target cells. Inhibition was observed with macrophages (Mø): spleen cell ratios as low as 0.01:1. It was independent from the activation status of Mø and was not MHC restricted. With respect to the mechanism, cell contact was essential. A cold target mechanism, reflected by some binding, but not killing, of NK cells by Mø was of minor influence. Spontaneously by Mø released soluble mediators could be excluded, nor was any soluble mediator released upon contact of Mø with spleen cells, but NK activity could be partly inhibited by supernatants from cocultures of Mø with adherent growing target cells.

Animals↗
PubMed1980

Organ-related and malignancy-associated reactivity of cancer patients' leucocytes: a leucocyte migration study with tumour and foetal extracts.

Leucocytes from patients with a variety of tumours including gastric, colorectal, lung, kidney and mammary cancer, were tested in the leucocyte migration test (LMT) against organ-related and non-organ-related tumour and foetal extracts. The reactivity of cancer patients' leucocytes against a panel of organ-related tumour extracts was found to be 71-93%, depending on the tumour system tested. Cross-reactivity with a panel on non-organ-related tumour extracts was found in 0-38% of patients. Corresponding patterns of reactivity were obtained by testing patients' leucocytes against human foetal organ extracts; pathological migration indices (MI) were found in 70% of tests in which patients' leucocytes were reacted with organ-related extracts, and in 16% of tests with non-organ-related extracts. The data strongly support the concept that patients' leucocytes are sensitized to cross-reactive foetal determinants of organ-related specificities. Furthermore, it is proposed that foetal extracts as inducers of lymphokine production in presensitized lymphocytes could be used efficiently and reproducibly as a source of foetal antigen, as well as in the clinical application of the LMT procedure.

Adult↗
PubMed1980

Lack of correlation between carcinoembryonic antigen content of tumor extracts and leukocyte migration reactivity of tumor patients.

Tumor extracts varying in carcinoembryonic antigen (CEA) content (0.4--2,280 ng/mg protein) did not affect the reactivity of cancer patients' leukocytes in the leukocyte migration inhibition test (LMIT). In addition, variations in the plasma CEA levels of tumor-bearing leukocyte donors did not influence the frequency of significant LMIT reactivity.

Adenocarcinoma↗
PubMed1980

Specific cytotoxicity in vitro by T-cell-enriched lymphocyte subpopulations from rats bearing chemically induced but not spontaneous tumors.

Effector cells from inbred BD X and WAB rats bearing either spontaneously arising or chemically induced tumors were cytotoxic for target cells of both kinds of tumor. The level of cytotoxicity of tumor-bearing animals regularly surmounted that of natural cytotoxicity observed in age-matched untreated controls. These findings were obtained by a visual-countin microcytotoxicity assay (48 hr) and by a 51Cr label assay (12 hr). Cytotoxicity by tumor-bearing rat effectors was directed against the homologous tumor target cell line, different tumor cells of the same inbred rat strain, tumor cells derived from allogeneic rats, and fetal fibroblasts, but not against adult fibroblasts. Separation of lymphocytes by rosetting with sheep red blood cells (SRBC) loaded with either antiimmunoglobulin or anti-SRBC or with anti-SRBC and complement revealed that cross-reactive cytotoxiciy was confined to a non-T effector cell population, which was observed with lymphocytes from rats bearing either chemically induced or spontaneous tumors. Cytotoxicity directed exclusively against the tumor of the lymphocyte donors was exerted by the T-cell-enriched fraction. This element was completely absent in lymphocytes from animals bearing spontaneous tumors, but it was detected in lymphocytes from donors with chemically induced (immunogenic) tumors.

Animals↗
PubMed1980

Characterization of natural cytotoxicity in vitro in a spontaneous rat tumor model.

Spontaneous rat tumor cells were tested in a 12-hr Cr-release assay for susceptibility or resistance to cytolysis by lymphoid effector cells from untreated rats. Most target cells were intermediate to highly susceptible (up to 85% lysis at an effector-to-target ratio of 50:1), but we observed nonsusceptible target cells, too. Cold target inhibition experiments confirmed the susceptibility classifications obtained in the direct assay. The functional properties of effector cells paralleled closely the known properties of natural killer cells. The NK responsiveness of various rat strains did not coincide with the incidence of spontaneous tumors.

Aging↗
PubMed1979

Sensitization of leukocytes of cancer patients against fetal antigens: leukocyte migration studies.

Hypertonic extracts from human fetuses (10--22 wk of gestation) were used to test the sensitizaton of leukocytes from cancer patients against fetal antigens in a direct, microcapillary tube assay system. Leukocytes were simultaneously exposed to a panel of allogeneic tumor extracts and a panel of fetal extracts. Leukocytes from 24 gastric cancer patients, 43 colorectal cancer patients, and 13 lung cancer patients were assayed with extracts obtained from gastric, colorectal, and oat cell carcinomas, respectively, and these extracts were also used with leukocytes from 41 patients bearing tumors of various other organs. Significant migration inhibition by tumor extracts was observed in 81.6% of the tests with gastric cancer, 67.4% of the tests with colorectal cancer, 69.0% of the tests with lung cancer, and 51.2% of the tests with other types of cancer. With fetal extracts, significant migration inhibition occurred in 58.3, 58.7, 59.6, and 54.9% of the tests, respectively. Reactivity against fetal extracts did not depend on the gestation age of the fetuses used for extraction. The conclusion was reached that the leukocytes of most of the cancer patients were sensitized against substances contained in fetal extracts irrespective of the type of tumor of the leukocyte donor. The cross-reactivity pattern suggested that 3-M KCl extracts of whole human fetuses contained a complex mixture of specificities related to the various fetal organs and tissues, which may have represented counterparts to most of the tumor-associated specificities.

Antigens↗
PubMed1978

High incidence of spontaneous transplantable tumours in BDX rats.

Untreated male and female BDX rats were observed over a period of 30 months for spontaneous tumours of a size suitable for transplantation. At the age of 13-30 months 60/97 animals developed tumours, 53 of which were considered as malignant, and 7 as benign tumours. The spectrum of malignant tumours included sarcomas of connective tissue and bone, skin carcinomas, tumours of the lung, the gastrointestinal tract, the genito-urinary tract, the mammary glands, the testis, the adrenal glands and also sarcomas of the neural system and malignancies of the lymphoreticular system. Out of 41 tumours implanted s.c., 34 of them could be passaged further. The primary latent period varied between 1 and 12 months.

Animals↗