Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells

Abstract

The invasion of normal tissues by cancer cells and the infiltration of tumours by macrophages to some degree involves active translatory movements by these cells. As necrosis is a common occurrence in solid tumours, we have studied the interactions of saline extracts from the necrotic regions of rat Walker-256 tumours and mouse Gardner lymphosarcomas on the transmembrane, in vitro migration of Walker and Gardner cancer cells, and rat and mouse peritoneal macrophages. Necrotic extracts enhanced cell migration independently of chemotactic activity, an effect which was partially reduced by Trasylol, an inhibitor of neutral proteases. Rat liver lysosomal preparations which contain lower levels of neutral proteases than necrotic extract, inhibited or had no effects on cell migration, and the lysosomal stabilizer hydrocortisone did not inhibit the action of necrotic extracts. The results indicate that necrosis may enhance the migration of cancer cells out of tumours and the migration of macrophages into them. The extracts act partially through their neutral protease content. In contrast to the enhancement of cell detachment by necrotic extracts, which previous work has shown to be partially mediated by their indirect effect in causing lysosomal labilization and which is partially inhibited by hydrocortisone, this indirect mechanism is not demonstrable in the enhancement of cell migration. The results indicate that the consequences of necrosis are worthy of consideration in attempts at understanding the biology of solid tumours.

Simulated Brain Tumor Growth Dynamics Using a Three-Dimensional Cellular Automaton

“…Previous research has shown that the expanding tumor increases both its cell loss (through necrosis/apoptosis and invasion) and its quiescent cell population (G /G arrested) due to a declining gradient of nutritional elements towards the center of the rapidly growing avascular mass (Folkman & Hochberg, 1973;Durand, 1976;Landry et al, 1981;Mueller-Klieser et al, 1986;Rotin et al, 1986;Freyer & Schor, 1989). At advanced tumor stages, volumetric growth slows down mostly due to the declining growth fraction (GF), an increasing cell loss and G -fraction (Turner & Weiss, 1980;Bauer et al, 1982;Freyer & Sutherland, 1985) caused by a lack of nutrition as well as an increasing con"nement pressure.…”

Emerging Patterns in Tumor Systems: Simulating the Dynamics of Multicellular Clusters with an Agent-based Spatial Agglomeration Model

“…apoptosis/ necrosis) linked with an increased level of hostile toxic metabolites per lattice site. For example, it has been demonstrated that low pH inhibits cell proliferation and contributes to cell death and necrosis within solid tumors, which in turn may induce tumor cells to migrate to more favorable locations (Tannock & Rotin, 1989;Turner & Weiss, 1980). In the following section we review some relevant modeling work.…”

Differences in surface expression of WGA-binding proteins of cells from a lymphosarcoma and its liver metastases

“…Aliquots of membranes and cell homogenates were assayed for 5' nucleotidase activity (Douglas et al, 1972), acid phosphatase activity (Turner & Weiss, 1980) and DNA content (Munro & Fleck, 1966). The mean specific activity of 5' nucleotidase from the membrane preparations was 3.5umolh-'mg-' protein, a value that was 5-6 times higher than the specific activity of this enzyme in the homogenate.…”