Gabriel J. Gasic

Thrombogenic activity of mouse and human tumors. Effects on platelets, coagulation, and fibrinolysis, and possible significance for metastases.

Twelve mouse tumors and 29 human malignancies were assayed in vitro for their capacity to aggregate platelets and induce release of radiolabelled serotonin, and for their ability to coagulate blood plasma and digest the fibrin clot. It was discovered that many human and mouse tumors can induce release of radiolabelled serotonin but that the quantitative relationships between this activity of tumors and their capacity to aggregate platelets was variable, permitting tumors to be classified into 3 different types. The procoagulant and fibrinolytic activity was also quite variable. Since no correlation was found between the 4 assayed tumor activities they appear to be independent, separate thrombogenic properties of tumors. Although the information gathered by this study is still fragmentary, some speculations can be made about the role of these activities in treatment of malignant tumors and in determining patterns of body distribution and control of metastases. An 12 Mäusetumoren und 29 menschlichen Tumoren wurden in vitro die Plättchenaggregation, die Serotoninfreisetzung aus Thrombocyten, die Gerinnungssowie die Fibrinolyseaktivität untersucht. Dabei stellte sich heraus, daß menschliche Tumoren und Mäusetumoren zwar die Serotoninfreisetzung induzieren können, das Verhältnis dieser Aktivität zu der Plättchenaggregationsfähigkeit jedoch nicht konstant war und eine Einteilung der Tumoren in drei verschiedene Typen zuließ. Die gerinnungsfördernde und die fibrinolytische Aktivität waren ebenfalls unterschiedlich. Da zwischen den vier untersuchten Aktivitäten keine Korrelation bestand, scheinen sie voneinander unabhängige thrombogene Tumoreigenschaften zu sein.

Effects of trypsin on the platelet-aggregating activity of mouse tumor cells

Abstract A platelet-aggregating factor is found in cells of two mouse tumors and in cell-free supernatants released spontaneously by tumor cells. The factor disappears from cells after trypsin treatment and its recovery in the cell-free supernatant depends on the degree of cell trypsinization. Activity of cells regenerates during subsequent incubation by a process requiring protein synthesis. The latter, and the fact that the non-dialyzable cell-free material is sensitive to heat and trypsin, suggest that it is a protein or a protein complex.

REMOVAL OF PAS POSITIVE SURFACE SUGARS IN TUMOR CELLS BY GLYCOSIDASES.

Summary Structural components of the coat of fixed TA3 tumor cells are stained both by the Hale and the PAS procedures. The Hale positive material can be removed by active neuramidase, indicating the presence of neuraminic acid. The PAS positive component is not influenced by lipid extraction or by diastase digestion and is only slightly affected by neuramidase. However, it is strongly affected by an enzyme preparation from Clostridium perfringens, containing a mixture of glycosidases. By specific blocking of individual glycosidases in the incubation medium, it was determined that galactose and acetyl-galactosamine are important components for the PAS positivity of the cell coat. Fucose is of less significance and perhaps less abundant than other PAS positive sugar units. N-acetyl-hexosaminidase from fungi of Genus Chalaropsis was also active against the PAS positive cell coat but differed from the glycosidases of CI. perfringens in that it did not require the previous removal of the Hale positive component and was not blocked by N-acetyl-galactosamine, galactose, and fucose.

Lysosomes in the Renal Papillae of Rats: Formation Induced by Potassium-Deficient Diet

Lysosomes appeared in the cytoplasm of cells of the renal papillae of rats fed on a potassium-deficient diet. The lysosomes were identified by their morphologic appearance when examined by electron microscopy, and by their acid phosphatase activity shown by both light and electron micro-scopic examination of Gomori-treated tissue.

Mechanisms of Platelet Aggregation by Murine Tumor Cell Sheddings

Cells from a variety of animal and human neoplasms can induce the aggregation of platelets in plasma (1–3). While the mechanism of this effect has not been fully elucidated preliminary evidence suggests that several mechanisms may exist. With human tumor cells platelet aggregation may be induced via mechanisms involving the leakage of tumor cell ADP (2, 4, 5; see also Chapters 11 and 12). In rodents aggregation may occur with both whole cells and cell sheddings. This suggests that the aggregating activity of intact cells is mediated by the spontaneous release of some subcellular component. We found that a mixture of membrane vesicles and cytoplasmic dense granules were shed (6). Normal cells are also capable of shedding a small amount of material which is much less active in platelet aggregation (6,7).

Mucopolysaccharides of Renal Collecting Tubule Cells in Potassium Deficient Rats.

Summary The granules which appear in the collecting tubule cells of potassium deficient rats give a positive reaction with both the Hale iron technique and the PAS stain. The capacity for Hale staining is removed after exposure to receptor destroying enzyme or neuraminidase, but not by hyaluronidase, cathepsin, hot chloroform methanol extraction, or exposure to amylases. The Hale staining was intensified after pepsin, trypsin, or chymotrypsin treatment. It is concluded that the granules contain an acid mucopolysaccharide, which probably contains sialic acid side groups, and that the acid mucopolysaccharide may be masked by protein, which can be uncovered by the action of pepsin, trypsin, or chymotrypsin.