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Biomedical subjects

M M Mareel

Publications and source records attributed to M M Mareel.

At least 91 records · Page 5Linked to original sources
PubMed1981

Invasiveness of malignant ST/A mouse lung cells in vitro.

ST/A mouse lung cells underwent apparently spontaneous malignant alteration in tissue culture. We have compared the capacity of these cells to form malignant tumours in syngeneic animals with their behaviour in vitro. ST-L1, ST-L22, and ST-L104 cells were malignant, whilst ST-L108 and ST-L109 cells were not. ST-L1 and ST-L22 cells showed anchorage-dependence of growth, whilst ST-L104, ST-L108 and ST-L109 cells did not. ST-L22, ST-L104, ST-L108 and ST-L109 performed directional migration from a spheroid explanted on glass. This capacity was lost in ST-L1 cells, which produced so-called round-cell transformants. All but ST-L108 cells produced type C viral particles. The tumorigenic cell lines ST-L1, ST-L22 and ST-L104 invaded fragments of embryonic chick heart in three-dimensional culture, whereas the non-tumorigenic ST-L108 and ST-L109 cells did not. Furthermore, the histology of ST-L cells invading in three-dimensional culture resembled that of the invasive sarcomas which they produced in vivo. The present observations with ST-L cells confirm that invasiveness in three-dimensional culture is a reliable criterion for malignant of tissue culture lines.

Animals↗
PubMed1981

Effect of anticancer agents on invasion of mouse fibrosarcoma cells in vitro.

The anti-invasive effect of microtubule inhibitors and other growth inhibitors was examined in confrontations of aggregates of mouse fibrosarcoma cells (MO4) with fragments of embryonic chick heart. The microtubule inhibitors Nocodazole and methyl [5-(2-(4-fluorophenyl)-1,3-dioxolan-2-yl)-1H-benzimidazole-2-yl] carbamate at 1 microgram/ml inhibited invasion. 5-Fluorouracil at 1 microgram/ml, mitomycin C at 0.1 microgram/ml and ionizing radiation at 50 Gy permitted invasion of fibrosarcoma cells into the heart tissue. These results suggest that tumors, the growth of which is effectively controlled, might continue to invade.

Animals↗
PubMed1981

Immunohistochemical study of embryonic chick heart invaded by malignant cells in three-dimensional culture.

MO4 mouse fibrosarcoma cells, B16 mouse melanoma cells, HeLa human cervical carcinoma cells, and LICR (LOND)-HN-4 human laryngeal carcinoma cells were shown to invade into precultured fragments of 9-day-old chick cardiac muscle in three-dimensional culture. Paraffin sections from such cultures were stained with an antiserum against chick heart following the unlabeled antibody enzyme method. The immunostaining demonstrated (1) differences in the rate and the way by which the four types of malignant cells occupied and replaced the chick cardiac muscle, and (2) the phagocytic activity of the four types of invading cells in three-dimensional culture.

Animals↗
PubMed1980

Phagocytic capacity of invasive malignant cells in three-dimensional culture.

To study the phagocytic capacity of invasive malignant cells, fragments of the hypoblast from chick blastoderms were confronted in three-dimensional culture with spheroidal aggregates of 1) malignant virally transformed C3H mouse cells (MO4), 2) HeLa cells and 3) embryonic chick heart cells. The hypoblast was used because it contains yolk, a marker that is absent in the confronting cells and that can be identified histologically and ultrastructurally. The confronting tissues were incubated on semi-solid agar-agar medium or in fluid medium on a gyrotory shaker. Cultures were followed for 1 to 7 days by stereomicroscopy, cinemicrophotography, light and transmission electron microscopy. Confrontation with MO4 cells of HeLa cells, known to be invasive in vitro, led to complete disappearance of the hypoblast. The fragments of hypoblast were well conserved when cultured alone or confronted with aggregates of chick heart cells. Degeneration of the hypoblast is shown at the area of contact with MO4-cell or HeLa-cell aggregates, in contrast to heart cells. Filopodia-like extensions from the MO4 or HeLa cells penetrate intercellularly, transcellularly and intracellularly into the hypoblast. Phagosomes, containing yolk and unidentified debris are observed in MO4 cells and in HeLa cells, but not in heart cells. These observations demonstrate the phagocytic capacity of invasive malignant cells.

Animals↗
PubMed1980

Effect of anticancer agents on directional migration of malignant C3H mouse fibroblastic cells in vitro.

Invasion of malignant cells was considered as a target for therapy. The effect of various anticancer agents, which were known to permit or to prevent invasion in vitro, on the growth and on the directional migration of virally transformed malignant C3H mouse fibroblastic cells (MO4) was examined. The increase of the diameter of spheroidal aggregates of MO4 cells in individual shaker culture was used as an index of growth. The mean diameter of the circular area covered by cells migrating from an aggregate explanted on glass, the number of cells in the periphery of this area, the height of the central part of the aggregate, the microcinephotographic aspect of migrating cells, and the immunocytochemistry of the cytoplasmic microtubular complex were considered as indices of directional migration. Ionizing radiation (5,000 and 20,000 R), and 5-fluorouracil (0.1, 0.5, and 1 microgram/ml), known to permit invasion, inhibited growth but allowed directional migration. Nocodazole (0.1 and 1 microgram/ml), known to prevent invasion, interfered with both growth and directional migration. These observations showed that various agents which affected the growth of aggregates of MO4 cells had different effects on the directional migration of these cells; they suggested that proliferation and migration were unrelated cellular activities. The assay for directional migration of cells from a spheroidal aggregate explanted on glass is proposed for the screening of potential antiinvasive agents.

Animals↗
PubMed1978

Confronting subsurface cisternae and desmosomes in HELA monolayer cultures.

Confronting subsurface cisternae (CSC) and desmosomes are abundant at sites of parallel apposition of plasma membranes in confluent epitheloid monolayers of HeLa cells. Both structures are absent in young and subconfluent cultures, where stable intercellular contacts do not occur. They first appear when the plane of intercellular contact approaches towards the vertical; they disappear when cells separate spontaneously at superconfluency or by treatment with EDTA. The structure of CSC, lacking ribosomes at their side facing the plasma membrane, might fit the production of glycoproteins involved in intercellular adhesion.

Cell Separation↗
PubMed1978

Effect of microtubule inhibitors on malignant invasion in vitro.

The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 microgram/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-1-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 microgram/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 microgram/ml) plus the microtubule inhibitor Nocodazole (1 microgram/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 microgram/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.

Benzimidazoles↗
PubMed1977

Wound healing in the primitive deep layer of the young chick blastoderm.

Wound healing in the primitive deep layer of stage 4 chick blastoderms was studied in vitro by cinemicrophotography of living cultures and by photomicroscopy, scanning- and transmission electron microscopy after fixation. Experimental wounds with an average diameter of 0.3 mm healed completely within 2 to 4 h through migration of the cells at their rims. Healing occurred in mesenchyme-free areas, providing us with a purely epithelial reaction. The rim cells of the primitive deep layer formed extensions at their free flank, described as fila, filopodia, lamellae and lamellipodia. They were already present in blastoderms fixed at the earliest after the intervention. This reaction was ascribed to the elimination of a normal fellow cell at the side of the rim cell facing the defect. Movement of the rim cell ceased upon meeting another cell with the same polarity. At this moment lamellipodia disappeared as suddenly as they had formed, and the number of fila and filopodia decreased. We believe that the chick blastoderm's primitive deep layer might be appropriate for analysis of the factors governing primary epithelial wound healing.

Animals↗
PubMed1974

A study on the mechanism of intercellular adhesion. Effects of neuraminidase, calcium, and trypsin on the aggregation of suspended HeLa cells.

Aggregation of suspended HeLa cells is increased on removal of cell surface sialic acid. Calcium ions promote aggregation whereas magnesium ions have no effect. The calcium effect is abolished by previous treatment of the cells with neuraminidase. Trypsinization of the HeLa cells followed by thorough washing diminishes the rate of mutual cell aggregation. Subsequent incubation with neuraminidase restores the aggregation rate to the original value before trypsin treatment. Cells which had acquired a greater tendency for aggregation after removal of peripheral sialic acid lose this property when subsequently treated with trypsin. Calcium ions have no aggregative effect on trypsinized cells. In contrast to HeLa cells, aggregation of human erythrocytes was not increased after treatment with neuraminidase or on addition of calcium. The results with HeLa cells are interpreted as follows: (a) Trypsin-releasable material confers adhesiveness upon the cells. (b) The adhesive property of this material is counteracted by the presence of cell surface sialic acids. (c) Calcium ions exert their effect by attenuating the adverse effect of sialic acid.

Calcium↗
PubMedDate not supplied

Effect of temperature on invasion of MO4 mouse fibrosarcoma cells in organ culture.

Invasion by MO4 mouse fibrosarcoma cells into fragments of embryonic chick heart or lung in organ culture was studied histologically and ultrastructurally at various temperatures between 12 and 40 degrees C. Invasion was absent for at least 7 days at or below temperatures of 29 degrees C. Invasion was invariably observed at or above 30.5 degrees C. Differences in invasion between 29 and 30.5 degrees C could not be ascribed to differences in growth, migration, or microtubule assembly/disassembly of MO4 cells. Neither could they be explained through differences in the attachment of MO4 cells to the heart fragments. Possible explanations for the absence of invasion at lower temperature are: altered resistance of the extracellular matrix in heart or lung fragments, and deficient expression of fucosylated glycoproteins at the surface of MO4 cells. A population of MO4 cells plated from the parent line and adapted to grow at 28 degrees C (MO(4)28 cell line) did not differ in invasiveness from the parent MO4 cells. We conclude that the temperature dependence of invasion in organ culture might indicate as yet unexplored aspects of the mechanisms of tumour invasion.

Animals↗
PubMedDate not supplied

(+)-Catechin inhibits the invasion of malignant fibrosarcoma cells into chick heart in vitro.

(+)-Catechin, a flavonoid extractable from higher plants and trees, inhibits the invasion of malignant MO4 fibrosarcoma cells into embryonic chick heart fragments in vitro. This inhibition is maximal at a drug concentration of 0.5 mM. The growth of the MO4 cells is only partly inhibited at such a concentration, and the effect can hardly be ascribed to an irreversible cytotoxicity of the drug to the host tissue. Pretreatment of the host tissue with the drug seems to be a prerequisite for the inhibitory action, which suggests that the anti-invasive effect is at least partly mediated by the condition of the heart tissue. We hypothesize that the collagen-stabilizing effect of (+)-catechin is the key to the explanation of its anti-invasive properties.

Animals↗
PubMedDate not supplied

Invasiveness and tumorigenicity of MO4 mouse fibrosarcoma cells pretreated with microtubule inhibitors.

MO4 cell aggregates with a diameter of 0.3 mm produced invasive fibrosarcomas after s.c. implantation into the pinna of syngeneic mice. Histology of pinnae fixed 10 min to 5 days after implantation of an aggregate suggested that the tumour was produced by the cells that invaded during the first day, and that the cells remaining in the aggregate were eliminated by the reaction of the host. Before implantation we have pretreated MO4 cell aggregates with 1 microgram/ml of the microtubule inhibitors Nocodazole (ND) and vincristine (VCR), known to inhibit both proliferation and invasion, and with 1 microgram/ml 5-fluorouracil (5-FU), known to inhibit proliferation but not invasion. Tumorigenicity was significantly reduced after treatment with ND or VCR, as compared to treatment with 5-FU or to controls. Histology of pinnae fixed 10 min to 3 days after implantation showed absence or scarceness of invasive MO4 cells after pretreatment with ND or VCR, in contrast with controls or with aggregates pretreated with 5-FU. The effect of ND, VCR and 5-FU on the growth of aggregates in culture on gyrotory shaker was reversible within 1 and 2 days respectively. After treatment with ND or VCR slight alterations in the function of the cytoplasmic microtubule complex remained visible during 3 days in cells migrating from an aggregate explanted on glass. Confrontation of pretreated aggregates with fragments of embryonic chick cardiac muscle in three-dimensional culture indicated that the anti-invasive effect of ND or VCR was reversible in vitro. We concluded that a delay of invasiveness caused by pretreatment with ND or VCR provided the host with the opportunity to eliminate MO4 cells implanted s.c. into the pinna.

Animals↗