Some mechanisms involved in cancer cell detachment by necrotic material.

Abstract

AbstractFactors influencing cell detachment are thought to play a role in metastasis and invasion. Previous studies on cylinders punched from Walker 256 (W‐256) tumors growing in rats showed that detachment of viable cancer cells was facilitated by their proximity to necrotic regions and exposure to a necrotic extract. By the use of pure cultures of W‐256 cells, it is shown that necrotic extracts which are rich in lysosomal hydrolases act directly on W‐256 cells, facilitating their in vitro detachment. Lysosomal enzymes have previously been shown to facilitate cell detachment. The partial inhibition of this process by hydrocortisone suggests that the extracts also act by labilizing the W‐256 cell lysosomes; this enzyme release is also demonstrable by direct assay. Although secondary lysosomes could not be visualized in the W‐256 cells, both they and macrophages release lysosomal hydrolases on freeze‐thawing, and could both account for the high enzyme content of the necrotic regions, by a process of continuous secretion and/or cell input. Histologic examination of perinecrotic and peripheral regions of tumors showed a higher proportion of macrophages in the former, which is thought to be mainly due to differential trapping of the macrophages. The results emphasize the functional properties of necrotic regions of tumors and the necessity of referring to specific regions of the same tumor when referring to its metastatic and other properties.