Susceptibility to NK cell lysis is abolished in tumor cells by a factor which restores their contact inhibited growth

Abstract

It is well recognized that physical contact between natural killer (NK) cells and tumor targets is necessary for cell lysis. Therefore, any modulation of the tumor cell surface that alters intercellular contact could affect NK cell cytotoxicity. To examine this hypothesis, a contact inhibitory factor (CIF), which had been shown to restore contact inhibition of growth to several malignant cell lines was tested for its ability to render such cells immune to recognition by NK cells. When three NK-sensitive melanoma and two NK-sensitive colon carcinoma targets were cultured with CIF, they did not only change morphologically, but also showed a 70% to 95% reduction in their sensitivity to lysis by NK cells. In addition, K562 cells, which grow in suspension and do not permit a morphologic evaluation of the CIF effect, also became resistant to lysis by NK cells after culture with CIF. CIF did not reduce the viability nor the cytotoxicity of NK cells. CIF did not contain interferon nor did the CIF-treated targets induce the production of interferon during the cytotoxicity assay. It is concluded that restoration of contact inhibition of growth and resistance to NK cell lysis are cell surface phenomena that may run in parallel.

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis

“…We believe this decrease in G 2 /M population of cells in the presence of hOGG1 is due to the protection this protein imparts to 2-MEinduced damage and not due to the regulation of hOGG1 itself, as it is well established that the hOGG1 gene is not regulated by cell cycle and is constitutively expressed (Dhenaut et al, 2000(Dhenaut et al, , 2001. Furthermore, cytotoxic effects of 2-ME studied by other groups showed an increase in LDH release (Nabi et al, 1986;Kachadourian et al, 2001), in this study we found that the presence of recombinant hOGG1 protects the cells from the cytotoxic effects of 2-ME based on our LDH data. Thus, our results show that 2-ME-induced damage to mtDNA may contribute to a decrease in cellular survival, induction of cell cycle arrest, mitochondrial membrane hyperpolarization and apoptosis via the Fas activation.…”

Contact‐inhibitory factor induces alterations in the distribution and content of specific cytoskeletal elements in an established line of rat hepatic tumor cells

“…CIF, a diffusible substance found in the conditioned medium of revertant (contact-inhibited) hamster melanocytic cells (Lipkin and Knecht, 1974), mediates certain changes in morphology, growth and differentiation of various cultured tumor cells. Such alterations include: (a) restoration of contact inhibition, (b) regain of anchorage-and serum-dependent proliferation, (c) induction of pigment-cell differentiation antigens on mouse and hamster melanoma cells, and (d) reduced susceptibility of human melanoma, colon carcinoma, and erythroleukemia cells to lysis by NK cells Knecht, 1974, 1976;Lipkin et al, 1978Lipkin et al, , 1985Lipkin et al, , 1986Nabi et al., 1986). CIF reduces cell proliferation by initiating a GI arrest, or at least a prolongation of this cell-cycle phase (Lipkin and Knecht, 1976).…”