Biomedical subjects

N Paweletz

Publications and source records attributed to N Paweletz.

132 records · Page 8Linked to original sources

PubMedDate not supplied

Ultrastructural analysis of experimentally induced invasion in the rat lung by tumor cells metastasizing lymphatically.

The colonization of the lung by the rat tumor cells BSp73 ASML which have the ability to metastasize via the lymphatic system was studied at the ultrastructural level. Tumor cells arriving in the lung after i.v. injection become transiently embolized; within hours, however, they begin to extravasate from the blood capillaries. Swelling cellular protrusions open a limited area between endothelium and basal lamina through which tumor cells erupt. Tumor cells then form metastases in the interstitial tissue and, in an apparently lymphotropic action, intravasate the lymphatic vessels in a similar manner to a reverse diapedesis-like process. Within the lympatic system they settle, spread, and build up extensive tumor foci particularly in the subpleural region.

Animals↗

PubMedDate not supplied

Experimental approaches to problems of invasion and metastasis.

The highly metastasizing ASML cells and the non-metastasizing AS cells, arisen as spontaneous tumors of the rat, were confronted with rat lung tissue in vitro. Small cubes of the lung were allowed to heal their cut edges, then tumor cells were added. Both tumor cell types adapted their shape to the environment, penetrated the superficial layer of lung cells, either of epithelial or of fibroblastoid character and settled on the basal lamina, which, however, was not pierced. In a second set of experiments the tumor cells were inoculated intravenously into the living animal. The lung loaded with tumor cells was excised and cut into cubes which were then incubated in vitro. Here also both tumor cell types exhibited an invasive behavior but the basal lamina of the vessels in which the tumor cells have been arrested was not penetrated. These data indicate that tumor cell behavior is strongly dependent on the environment and the complete invasion or extravasation must be considered as an inducible process.

Animals↗

PubMedDate not supplied

Invasive activities of metastasizing and nonmetastasizing tumor cell variants in vitro. II. Studies on confrontations with aorta, vein, ductus thoracicus, diaphragm, and lung.

In continuation of a previous paper (1), we have prolonged the time of confrontation of two rat tumor cell variants (BSp73 AS and ASML) with normal epithelial cells and broadened the spectrum of confrontation partners. In addition to the aorta we have also used small veins, the ductus thoracicus as a lymphatic vessel, the diaphragm, and lung fragments. The organ sections were preserved for a longer period of time by incubating them in a gyratory shaker. Under these conditions the vessel material and diaphragm remained morphologically intact for up to 12 hrs; lung cubes concealed the cut surfaces by immediate wound healing, and were preserved intact for up to 40 days. All endothelia and the mesothelium of the diaphragm were destroyed by the nonmetastasizing AS cells, but the basal lamina remained intact by morphological criteria even after 18 hrs of exposure to the AS cells. The metastasizing ASML cells attached by filopodia mostly to the basal lamina of the vessels, but were unable to destroy neither the endothelia nor the basal lamina. The superficial cell layers of the lung cubes, however, were penetrated by the cells of both tumor lines, but to a different degree.

Animals↗

PubMedDate not supplied

Studies on confrontation of different tumor cells with human diploid fibroblasts.

Cells of two HeLa sublines (HeLa 1 and HeLa S) and of the rat tumor cell variants AS and ASML were confronted with human diploid lung fibroblasts (WI38). This "bilayer" system was established to study various cell-cell and cell-substrate interactions including the adhesion and spreading process of tumor cells. In this model system we could demonstrate that the behavior of different tumor cells is dependent on the environment. On the other hand, we could find an independence from species or strain barriers. This was demonstrated in the xenogenic combination of rat tumor cells and human fibroblasts.

Animals↗

PubMedDate not supplied

Invasive activities of metastasizing and nonmetastasizing tumor cell variants in vitro.

Pieces of the endothelium of the aorta of BDX rats were confronted with two syngeneic-tumor-cell variants. While the AS variant is non-metastasizing, the ASML cells metastasize spontaneously via the lymphatic vessels. By means of scanning-electron microscopy the adhesion phenomena and the various stages of invasive activity of the non-metastasizing variant (AS) as well as the retraction of the endothelial cells depending on the time of confrontation were studied. Though the metastasizing variant (ASML) adhered firmly to the endothelium, we found neither signs of invasive activity of these tumor cells nor retraction phenomena of the endothelial cells. Aggregates of AS- and clusters of ASML-cells, respectively, behaved in exactly the same way as single cells: while the ASML-clusters remained inactive, the AS-aggregates exhibited invasive activities. Those cells which were in intimate contact with the endothelium started to leave the aggregate, thereby forming a foot-like layer beneath the rest of the aggregate; these cells began to invade.

Animals↗

PubMedDate not supplied

Induction of premature mitosis in cells blocked in S-phase: possibilities of its use in cancer therapy.

Oncogenesis leads to weak regulations of many cell cycle checkpoints. This could be useful for cancer therapy. To test this assumption, five human malignant cell lines were used to induce premature mitosis by overriding the S-phase control, which ultimately leads to cell death. Two cell lines showed a significantly high frequency of premature mitotic cells induced by okadaic acid; whereas the others did not. One cell line, although having a high cyclin B level in cells blocked in S-phase, failed to show premature mitosis. The cyclin B level in cells blocked in S-phase alone could not explain the differential behavior of the cell lines. It was observed that in addition, the activation of cdc25 in these cells could also play an important role in the induction of premature mitosis in such cells.

Cell Adhesion↗